Children with Mycoplasma pneumoniae infection in Taiwan: Changes in molecular characteristics and clinical outcomes.

BACKGROUND: Mycoplasma pneumoniae is a pathogen that causes respiratory diseases in children. Infections caused by M. pneumoniae are usually self-limited but occasionally can be severe. We observed emerging cases of severe mycoplasma infection requiring extracorporeal membrane oxygenation (ECMO). Thus, we investigated chronological changes in the molecular features of the M. pneumoniae and its clinical impacts among the pediatric population. METHODS: From 2011 to 2019, respiratory samples were collected from patients younger than 18 years old with pneumonia in a tertiary children's hospital. Focused multiple-locus variable number of tandem repeats analysis (MLVA) typing was performed on samples positive for M. pneumoniae in 2016 and 2019. Clinical data from the patients' electronic medical records were collected. We described the annual trend of macrolide resistance and MLVA type and analyzed the associations between clinical manifestations and MLVA types. RESULTS: The percentage of macrolide-resistant (MLR) M. pneumoniae gradually increased from 22% (27/122) in 2015 to 70% (82/117) in 2019. Among the MLRM. pneumoniae, the predominant strain shifted from type P (31% [13/42]) to type A (40% [19/46]). The demographics, initial presentations, and clinical courses of the subjects with MLRM. pneumoniae did not differ significantly between 2011 and 2019. However, in 2019, two fulminant cases requiring venovenous ECMO were observed, which indicates that more attention to the clinical severity of MLRM. pneumoniae infections is warranted. CONCLUSION: Obtaining accurate information on macrolide susceptibility is crucial for physicians to initiate appropriate antibiotic treatment in a timely fashion. Although we could not identify significant differences among mycoplasma pneumonias caused by different MLVAs over a span of 9 years, the emergence of severe mycoplasma infections requiring ECMO was clinically significant, and further monitoring was required.

Risk Factors for Severe Respiratory Syncytial Virus Infection in Hospitalized Children.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of bronchiolitis and pneumonia in infants and young children. Starting in December 2010, RSV monoclonal antibody (RSV mAb) was endorsed by Taiwan National Health Insurance and given to children with prematurity and/or congenital heart diseases, which are considered high-risk factors for severe RSV diseases. Investigating other important contributing risk factors is warranted. METHODS: We conducted a cohort study at National Taiwan University Hospital to determine the rate of severe outcomes among children hospitalized due to RSV infection from 2008 to 2018. Adjusted for age, sex and birth cohorts born before and after RSV mAb endorsement, we identified risk factors for severe RSV infection, defined as the requirement of invasive ventilator support. RESULTS: There were 1985 admissions due to RSV infections. Among them, 66 patients (3.3%) had severe RSV infection. The proportion of severe RSV infections decreased significantly after RSV mAb endorsement. Multivariable analysis revealed that age <1.5 months and cardiovascular and congenital/genetic diseases were high-risk underlying conditions. In addition, bacterial coinfections, elevated creatinine levels and initial abnormal chest radiograph findings posed warning signs for severe RSV infection. CONCLUSIONS: Children younger than 1.5 months of age with cardiovascular or congenital/genetic diseases were predisposed to severe RSV infection and might benefit from RSV mAb prophylaxis.

Adverse events following immunization with the live-attenuated recombinant Japanese encephalitis vaccine (IMOJEV®) in Taiwan, 2017-18.

BACKGROUND: Japanese encephalitis (JE) is a significant public health concern in the Asia-Pacific region, with a case-fatality rate of around 20% for those who develop encephalitis. Mouse-brain derived vaccines against JE have been used in the publicly funded national immunization program (NIP) in Taiwan since 1968. They were replaced with a live-attenuated recombinant vaccine (JE-CV, IMOJEV®) in May 2017. We assessed reports of adverse events (AE) following the introduction of JE-CV into the Taiwan NIP to characterize its post-licensure safety profile. METHODS: AEs reported between 1 May 2017 and 31 December 2018 post vaccination with JE-CV were extracted from the National Adverse Drug Reactions (ADR) Reporting System, a passive surveillance system run by the Taiwan Food and Drug Administration. The report rates were calculated based on the number of doses distributed by the manufacturer during the assessment period. RESULTS: There were 51 AEs reported among 30 subjects (12 girls and 18 boys; mean age 25 months), with a reporting rate of 4.7 AEs per 100,000 doses distributed. The AEs occurred after a median of. 1-day post vaccination. Eight subjects had received concomitant vaccination with another vaccines. There were four serious AEs reported: febrile seizure, acute renal failure, viral respiratory tract infection, and injection site cellulitis. None of these serious AEs were classified as being causally related to JE-CV vaccination. CONCLUSION: These post-licensure AE surveillance data confirm the favorable safety profile of JE-CV.

Association of EV71 3C polymorphisms with clinical severity.

OBJECTIVES: Enterovirus 71 (EV71) may cause neurological and fatal cases. EV71 3C plays an important role on viral replication and possess proteolysis activity. To delineate pathogenesis of EV71 virulence, we studied EV71 3C genetics, protease activity and correlated the results with clinical severity. METHODS: EV71 cases were collected; 3C of EV71 was sequenced and linked with clinical severity. 3C protease activity, viral replication rates of EV71 infectious clones with different 3C and 3C interaction with host proteins were analyzed. RESULTS: The polymorphisms of EV71 3C at the 79th amino acid were associated with clinical severity. About 26% (62/234) patients infected by EV71 with wild-type 3C (T79) had neurological involvement but 78% (25/32) patients infected by EV71 with mutant 3C (T79V) did (p < 0.001). There was no significant difference of protease activity among the different 3C variants. EV71 with mutant 3C (T79V) had the highest viral replication rate and the mutant 3C (T79V) had weaker interaction with TRIM21, a component of antibody-dependent intracellular neutralization, than the other mutants (T79I and T79A). CONCLUSION: We found that 3C polymorphisms were associated with clinical severity and viral replication, which might be related to 3C interaction with important host proteins such as TRIM21.

Prognostic factors of health care-associated bloodstream infection in adult patients ≥40 years of age.

We investigated 401 geriatric patients and 453 middle-aged patients with health care-associated bloodstream infection (HABSI) at a medical center during January-December 2014. Compared with middle-aged patients, the geriatric group had higher 30-day mortality (31.2% vs 23.4%, P = .01). Body mass index, serum albumin concentration, Charlson comorbidity index score, vancomycin-resistant Enterococcus bacteremia, and high C-reactive protein levels predict poor outcomes for HABSI among adult patients.

Lack of Pertussis Protective Antibodies in Healthcare Providers Taking Care of Neonates and Infants in a Children's Hospital.

Contact tracing and seroepidemiologic studies were done after a premature baby contracted pertussis in a children's hospital. No infection source was confirmed. Four (3.5%) healthcare providers were positive for anti-pertussis IgM, while only 23% (26/113) were positive for IgG in a following survey. Pertussis vaccination for healthcare providers is needed.

Risk factors and outcomes of cytomegalovirus viremia in pediatric hematopoietic stem cell transplantation patients.

BACKGROUND: Cytomegalovirus (CMV) is a major pathogen causing significant mortality and morbidity in immunocompromised hosts. It is important to find risk factors associated with CMV viremia and its outcome. METHODS: We investigated the incidence, time of onset, risk factors for CMV viremia, and characteristics of CMV diseases in 57 pediatric patients receiving hematopoietic stem cell transplantation (HSCT). Between August 2011 and March 2014, cases of pediatric HSCT patients at the National Taiwan University Children's Hospital were reviewed. Viremia was identified by plasma CMV real-time polymerase chain reaction (RT-PCR) assay. RESULTS: Eighteen (32%) of the 57 patients developed CMV viremia at a median of 23 days post-HSCT (range -3 to +721 days). Eighty-nine percent (16/18) of CMV viremia occurred within 100 days posttransplantation. Four patients finally had CMV diseases (1 with CMV colitis and 3 with CMV pneumonitis) and one patient died of CMV pneumonitis complicated with pulmonary hemorrhage and sepsis. Significant risk factors associated with CMV viremia via univariate analysis include older age (p = 0.03), leukemic patients [odds ratio (OR): 5.2, 95% confidence interval (CI): 1.52∼17.7, p = 0.008), allogeneic HSCT (OR: 14.57, 95% CI: 1.76∼120.5, p = 0.002), antithymoglobulin (ATG) use before transplantation (OR: 5.09, 95% CI: 1.52∼16.9, p = 0.007), graft-versus-host disease (GvHD) (OR: 10.1, 95% CI: 2.7∼38.7, p < 0.001), and gastrointestinal GvHD (OR: 10.9, 95% CI: 2.72∼43.9, p = 0.001). CONCLUSION: In pediatric posttransplantation patients, CMV viremia mostly occurred within 100 days after transplantation. Risk factors associated with CMV viremia include older diagnostic age, leukemic patients, unrelated donor HSCT, pretransplant ATG use, GvHD, and gastrointestinal GvHD.

Risk factors associated with severe influenza virus infections in hospitalized children during the 2013 to 2014 season.

BACKGROUND: An outbreak of influenza virus infection occurred in Taiwan from October 2013 to May 2014. We conducted a clinical study to identify risk factors associated with severe influenza virus infections in children. METHODS: During the outbreak period, data from 110 hospitalized children with influenza virus infection were collected. We analyzed the data, the need for intensive care, and patient outcome to identify clinical features and risk factors of severe infections, defined as the need of intensive care. RESULTS: Of the 110 inpatients, there were 57 male and 53 female patients; the median age was 2.6 (interquartile range, 1.0-6.3) years. Nineteen patients required intensive care and two patients died. Children who were underweight (p = 0.01) or those with neuromuscular disease (p = 0.007) and digestive tract disease (p = 0.03) were prone to severe infection. Occurrence of seizure (p = 0.004), conscious disturbance (p = 0.02), or low oxygen saturation at admission (p = 0.04) predicted the need for intensive care. Higher initial absolute neutrophil count (p = 0.02) and patch or pleural effusion on chest X-ray examination (p = 0.02) were associated with severe infection. In the multivariable analysis, digestive tract disease [p = 0.03; adjusted odds ratio (OR), 12.37; 95% confidence interval (CI), 1.28-119.43], seizure (p = 0.001; adjusted OR, 49.54; 95% CI, 4.61-532.76) and conscious disturbance (p = 0.006; adjusted OR, 131.61; 95% CI, 4.18-4141.64) were most significantly associated with severe influenza virus infection. CONCLUSION: Close monitoring of the important risk factors including underlying digestive tract diseases, seizure attack and conscious disturbance were recommended during the influenza season.