Yu-Chia Hsieh

Clinical manifestations and molecular epidemiology of necrotizing pneumonia and empyema caused by Streptococcus pneumoniae in children in Taiwan.

Recently, there have been increasing numbers of pneumococcal pneumonia cases, with their associated complications. We conducted a retrospective review to increase the understanding of childhood pneumococcal pneumonia. Seventy-one patients with pneumococcal pneumonia were identified. Forty (56.3%) of them developed complicated pneumonia. Multivariate analysis showed that presence of immature polymorphonuclear leukocytes in peripheral blood (odds ratio [OR], 3.67; 95% confidence interval [CI], 1.08-12.63), high C-reactive protein levels (>12 mg/dL) (OR, 5.24; 95% CI, 1.10-24.93), and no underlying disease at presentation (OR, 5.48; 95% CI, 1.06-28.25) were independent predictors of the occurrence of necrosis or/and abscess. Fourteen isolates (35%), which were genotypically identical and had the same pulsed-field gel electrophoresis pattern (serogroup 14, with MICs of penicillin of 0.1-0.5 mu g/mL), were significantly associated with complicated pneumonia (P=.047). Whether the virulence of antibiotic-resistant pneumococci is evolving deserves further investigation.

Influenza Pandemics: Past, Present and Future

Influenza A virus is well known for its capability for genetic changes either through antigen drift or antigen shift. Antigen shift is derived from reassortment of gene segments between viruses, and may result in an antigenically novel virus that is capable of causing a worldwide pandemic. As we trace backwards through the history of influenza pandemics, a repeating pattern can be observed, namely, a limited wave in the first year followed by global spread in the following year. In the 20th century alone, there were three overwhelming pandemics, in 1918, 1957 and 1968, caused by H1N1 (Spanish flu), H2N2 (Asian flu) and H3N2 (Hong Kong flu), respectively. In 1957 and 1968, excess mortality was noted in infants, the elderly and persons with chronic diseases, similar to what occurred during interpandemic periods. In 1918, there was one distinct peak of excess death in young adults aged between 20 and 40 years old; leukopenia and hemorrhage were prominent features. Acute pulmonary edema and hemorrhagic pneumonia contributed to rapidly lethal outcome in young adults. Autopsies disclosed multiple-organ involvement, including pericarditis, myocarditis, hepatitis and splenomegaly. These findings are, in part, consistent with clinical manifestations of human infection with avian influenza A H5N1 virus, in which reactive hemophagocytic syndrome was a characteristic pathologic finding that accounted for pancytopenia, abnormal liver function and multiple organ failure. All the elements of an impending pandemic are in place. Unless effective measures are implemented, we will likely observe a pandemic in the coming seasons. Host immune response plays a crucial role in disease caused by newly emerged influenza virus, such as the 1918 pandemic strain and the recent avian H5N1 strain. Sustained activation of lymphocytes and macrophages after infection results in massive cytokine response, thus leading to severe systemic inflammation. Further investigations into how the virus interacts with the hosts immune system will be helpful in guiding future therapeutic strategies in facing influenza pandemics.

Characterization of invasive isolates of Streptococcus pneumoniae among Taiwanese children

Accurate molecular surveillance is important in monitoring the dynamics of Streptococcus pneumoniae. A prospective study was conducted to collect invasive isolates of S. pneumoniae from children for genetic analysis from January 2004 to December 2006 in Taiwan. PCRs were performed to detect the zmpC and zmpD genes, both encoding a metalloprotease virulence factor in pneumococci, among these invasive isolates. During the study period, 68 invasive isolates of S. pneumoniae were obtained for analysis. Serotype 14 was the most common type isolated from children with invasive disease and was significantly associated with pneumonia (OR 3.1; 95% CI] 1.1-8.8; p 0.035). Serotype 23F was significantly associated with bacteraemia (OR 7.5; 95% CI 1.8-31.3; p 0.006). The seven-valent conjugate vaccine covered 83.8% of invasive isolates, but non-vaccine serotypes were more frequently isolated from patients with underlying diseases than from patients without underlying diseases (p 0.007 by Fishers exact test). Clonal complexes related to international clones Spain23F ST81, Spain6B ST95, England14 ST9, Taiwan19F ST236, Taiwan23F ST242 and Colombia23F ST338 accounted for 52.9% of invasive isolates. Dissemination of the penicillin-resistant clones ST876, ST46, ST76 and ST2889, which were first identified in Taiwan, was also found; 1.5% of these invasive isolates carried the zmpC gene, and 47.1% of these invasive isolates carried the zmpD gene. In conclusion, the spread of certain international clones and some domestic antibiotic-resistant clones resulted in invasive diseases among Taiwanese children.

Clonal Spread of Highly β-Lactam-Resistant Streptococcus pneumoniae Isolates in Taiwan

ABSTRACT This study aimed to evaluate the antimicrobial susceptibility profiles of 364 Streptococcus pneumoniae isolates and studied the genotypes of S. pneumoniae with high level β-lactam resistance in Taiwan. Clonal complexes related to Spain23F-1, Taiwan19F-14, and Taiwan23F-15 were responsible for the spread of isolates with high β-lactam resistance.

Seroprevalence and severity of 2009 pandemic influenza A H1N1 in Taiwan.

Background This study is to determine the seroprevalence of the pandemic influenza A H1N1 virus (pH1N1) in Taiwan before and after the 2009 pandemic, and to estimate the relative severity of pH1N1 infections among different age groups. Methodology/Principal Findings A total of 1544 and 1558 random serum samples were collected from the general population in Taiwan in 2007 and 2010, respectively. Seropositivity was defined by a hemagglutination inhibition titer to pH1N1 (A/Taiwan/126/09) ≥1:40. The seropositivity rate of pH1N1 among the unvaccinated subjects and national surveillance data were used to compare the proportion of infections that led to severe diseases and fatalities among different age groups. The overall seroprevalence of pH1N1 was 0.91% (95% confidence interval [CI] 0.43–1.38) in 2007 and significantly increased to 29.9% (95% CI 27.6–32.2) in 2010 (p<0.0001), with the peak attack rate (55.4%) in 10–17 year-old adolescents, the lowest in elderly ≥65 years (14.1%). The overall attack rates were 20.6% (188/912) in unvaccinated subjects. Among the unvaccinated but infected populations, the estimated attack rates of severe cases per 100,000 infections were significantly higher in children aged 0–5 years (54.9 cases, odds ratio [OR] 4.23, 95% CI 3.04–5.90) and elderly ≥ 65years (22.4 cases, OR 2.76, 95% CI 1.99–3.83) compared to adolescents aged 10–17 years (13.0 cases). The overall case-fatality rate was 0.98 per 100,000 infections without a significant difference in different age groups. Conclusions/Significance Pre-existing immunity against pH1N1 was rarely identified in Taiwanese at any age in 2007. Young children and elderly – the two most lower seroprotection groups showed the greatest vulnerability to clinical severity after the pH1N1 infections. These results imply that both age groups should have higher priority for immunization in the coming flu season.

Epidemiology and impacts of children hospitalized with pneumonia from 1997 to 2004 in Taiwan

Few studies have investigated the epidemiology and disease burden of childhood pneumonia in Taiwan, a middle‐income country.

The correlation between the presence of viremia and clinical severity in patients with enterovirus 71 infection: a multi-center cohort study

BackgroundEnterovirus 71 (EV71) is a great disease burden across the whole world, particularly in Southeast Asia. However, in recent decades, the pathogenesis of severe EV71 infection was not well understood. This study was aimed to investigate the correlation between the presence of viremia and the clinical severity of EV71 infection.MethodsWe organized a prospective cohort study and enrolled laboratory-confirmed EV71 cases in six tertiary care hospitals in Taiwan during the EV71 epidemic from 2011 to 2012. Blood samples were collected once in the acute stage, on the first day of admission. We used real-time RT-PCR to detect EV71 viremia. Demographical and clinical data were collected and the clinical severity was categorized into four grades. Data analysis was performed to identify the risk factors of viremia and the correlation between viremia and clinical severity of EV71 infection.ResultsOf the total 224 enrolled patients, 59 (26%) patients were confirmed to have viremia. Two-thirds (68%) of viremic cases were detected within the first three days of infection. Viremia occurred more frequently in children under the age of one year old (odds ratios [OR] 4.82, p < 0.001) but the association between the presence of viremia and complicated EV71 infection was not found (OR 1.02, p = 0.96). In the viremia group, patients had significantly more severe complications if viremia was detected after the third day of disease onset (26% vs. 5%, p = 0.03).ConclusionsViremia occurred more frequently in children under the age of one year and viremia detected beyond three days after the onset of disease correlated with more severe disease in EV71 patients.

Astrovirus Gastroenteritis in Children in Taipei

BACKGROUND/PURPOSE A prospective study was initiated to study astroviral infections in Taiwan. METHODS A total of 415 stool samples were collected and assayed for astrovirus antigen using an enzyme immunoassay. RESULTS Twelve (2.9%) stool samples from 12 patients were positive for astrovirus antigen. Most patients (8/12) had watery diarrhea which lasted for 2-6 days. The majority of patients recovered without specific treatment, except for two patients who were treated with antibiotics for possible bacterial infections. One patient developed chronic diarrhea and two episodes were nosocomially acquired. A clustering in the autumn and winter, with a peak in December (5/12), was noted. Growth on Caco-2 cells was performed for four specimens with positive astroviral RT-PCR results, and a characteristic cytopathic effect was observed after 4 days. Astroviral RNA was detected in six stool samples using RT-PCR. Five of six strains were serotype 1 and one strain was serotype 3. Sequence homology among the six strains was between 80.5% and 100%. A higher degree of homology (89.9-100%) was noted in the five strains of serotype 1. A phylogenetic study demonstrated two clusters in our strains and Oxford reference strain types 1 and 2. CONCLUSION Our study results provide further information about the prevalence and span of clinical spectra associated with astroviral infections in Taiwan. The current study showed that infection with astroviruses may be an important cause of gastroenteritis, as well as respiratory symptoms, in infants and children in Taipei.

Scarlet fever outbreak in Hong Kong, 2011

An outbreak of scarlet fever hit Hong Kong in 2011. At least 600 cases of scarlet fever have been reported in Hong Kong till the end of June 2011, with two resulting in deaths. The first fatal case, a 7-year-old girl, presented with fever, sore throat, vomiting, and skin rash on May 20. She consulted a private doctor first but her condition did not improve. She was referred and admitted to Queen Mary’s Hospital on May 27. Her condition further deteriorated and complicated with toxic shock syndrome. She passed away on May 29. The second fatal case, a 5-year-old boy, presented with fever from June 15. He was admitted to Princess Margaret Hospital on June 19 for sudden deterioration in condition. The boy developed toxic shock syndrome and passed away on June 21. He had consulted a general practitioner for chickenpox earlier. Further laboratory investigation showed that the isolates of Streptococcus pyogenes from both fatal cases belonged to different strains. Emm12 and emm1 were identified for both S pyogenes isolates. University of Hong Kong scientists said that they had discovered a mutation of the main isolates, making it more contagious and deadly. The new strain was more resistant to erythromycin and clindamycin, a resistance rate increasing from 10e30% previously to 60%, by picking up one or more genes from bacteria normally found in the human oral and urogenital tracts. Because Hong Kong and Taiwan are very close, both geographical location and people, it is quite common for people living in Taiwan to travel to Hong Kong, and thus,

Epidemiology and Clinical Characteristics of Listeria monocytogenes Bacteremia in a Taiwanese Medical Center

BACKGROUND/PURPOSE There have been many reported cases of Listeria monocytogenes bacteremia in Europe and the United States, but only a few from Taiwan. The present study was undertaken to analyze the clinical characteristics of patients with L. monocytogenes bacteremia in Taiwan. METHODS Patients with culture-confirmed L. monocytogenes bacteremia were identified at Chang Gung Memorial Hospital between January 2001 and December 2008. The clinical features and outcomes of the patients and the antimicrobial susceptibilities of the clinical isolates were analyzed. RESULTS Forty-three patients, including two newborn babies (4.7%) and 41 adults (95.3%), with at least one episode of Listeria bacteremia were identified. Forty-two (97.7%) of these patients had underlying diseases. Thirty-three patients (76.7%) had fever, 14 (32.6%) had experienced respiratory distress, and 11 (25.6%) had reported changes in consciousness. Twelve patients died within 14 days of infection, corresponding to a case-fatality rate of 27.9%. All the clinical isolates tested were susceptible to ampicillin, penicillin and vancomycin. CONCLUSION Most cases of L. monocytogenes infection occurred in adults with underlying diseases, especially malignancy, and only two cases of neonatal L. monocytogenes bacteremia were identified over the 8-year period. Penicillin, ampicillin and vancomycin could be used for the treatment of L. monocytogenes bacteremia, with the case-fatality rate lower for patients who received appropriate treatment.