Coronavirus disease 2019 (COVID-19) universal admission screening in patients and companions in Taiwan from May 2021 to June 2022: A nationwide multicenter study.

OBJECTIVE: Universal admission screening and follow-up symptom-based testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may play critical roles in controlling nosocomial transmission. We describe the performance of test strategies for inpatients and their companions during various disease incidences in Taiwan. DESIGN: Retrospective population-based cohort study. SETTING: The study was conducted across 476 hospitals in Taiwan. METHODS: The data for both testing strategies by reverse transcription-polymerase chain reaction for SARS-CoV-2 in newly admitted patients and their companions during May 2021-June 2022 were extracted and analyzed. RESULTS: The positivity rate of universal admission screening was 0.76% (14,640 of 1,928,676) for patients and 0.37% (5,372 of 1,438,944) for companions. The weekly community incidences of period 1 (May 2021-June 2021), period 2 (July 2021-March 2022), and period 3 (April 2022-June 2022) were 6.57, 0.27, and 1,261, respectively, per 100,000 population. The positivity rates of universal admission screening for patients and companions (4.39% and 2.18%) in period 3 were higher than those in periods 1 (0.29% and 0.04%) and 2 (0.03% and 0.003%) (all P < .01). Among the 22,201 confirmed cases, 9.86% were identified by symptom-based testing. The costs and potential savings of universal admission screening for patients and companions achieved a breakeven point when the test strategy was implemented in a period with weekly community incidences of 27 and 358 per 100,000 population, respectively. CONCLUSIONS: Universal admission screening and follow-up symptom-based testing is important for reducing nosocomial transmission. Implementing universal admission screening at an appropriate time would balance the benefits with costs and potential unintended harms.

Pilot validation of central line-associated bloodstream infection data in a voluntary surveillance system in Taiwan between October and December 2021.

Background: Central line-associated bloodstream infection (CLABSI) surveillance data are voluntarily submitted to the Taiwan Healthcare-associated Infection and Antimicrobial Resistance Surveillance (THAS) System. Validation of the CLABSI data is important to ensure the quality of surveillance data. We aimed to validate the CLABSI surveillance data reported to the THAS system. Methods: This study was a retrospective medical record review of patients with positive blood cultures admitted to the intensive care units (ICUs) of 13 participating hospitals between October and December 2021. An external validation team was convened to perform the validation process according to the standardised protocol and to record the reasons for misclassification. Discussion: During the study period, 688 patients with 1,238 positive blood cultures from 59 ICUs at 13 hospitals were evaluated. Among the 185 potential CLABSI events which met the THAS definition by either the external reviewers or the hospital reviewers, 24 (13.0%) events were identified by only the external reviewers, and six (3.2%) were identified by only the hospital reviewers, with an agreement rate of 83.8%. Using external reviewers as the gold standard, the pooled mean sensitivity and positive predictive value of CLABSI reporting were 86.6% (155/179) and 96.3% (155/161), respectively. Among the 37 misclassification episodes, missed case findings were the most common reason for misclassification (N=16, 43.2%). Conclusions: The CLABSI data reported to the THAS system are generally reliable. This study showed the need for ongoing validation processes and quality improvement to maintain the accuracy and validity of the surveillance data.

Excess mortality and long-term disability from healthcare-associated carbapenem-resistant Acinetobacter baumannii infections: A nationwide population-based matched cohort study.

BACKGROUND: Carbapenem resistance is perceived as a clinical challenge in the management of debilitated and immunocompromised patients who eventually will die from underlying diseases. We aimed to examine whether carbapenem resistance per se, rather than the underlying diseases, negatively affect outcomes, by comparing the excess mortality and morbidity from healthcare-associated infections (HAIs) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-susceptible A. baumannii (CSAB). METHODS: This was a nationwide retrospective matched cohort study of hospitalized patients in 96 hospitals which participated in Taiwan Nosocomial Infection Surveillance (TNIS). A total of 2,213 patients with A. baumannii HAIs were individually matched to 4,426 patients without HAIs. Main outcomes were excess risks for one-year all-cause mortality and one-year new-onset chronic ventilator dependence or dialysis-dependent end-stage renal disease. RESULTS: Excess one-year mortality was 27.2% in CRAB patients, compared with their matched uninfected inpatients, as well as 15.4% in CSAB patients (also compared with their matched uninfected inpatients), resulting in an attributable mortality of 11.8% (P <0.001) associated with carbapenem resistance. The excess risk associated with carbapenem resistance for new-onset chronic ventilator dependence was 5.2% (P <0.001). Carbapenem resistance was also associated with an extra cost of $2,511 per case of A. baumannii HAIs (P <0.001). CONCLUSION: Carbapenem resistance is associated with a significant disease burden in terms of excess mortality, long-term ventilator dependence, and medical cost. Further studies on effects of antimicrobial stewardship programs in decreasing this burden are warranted.

COVID-19 outbreaks in long-term care facilities-a nationwide population-based cohort study in Taiwan, May-July 2021.

BACKGROUND/PURPOSE: Long-term care facilities (LTCFs) are high-risk settings for the novel coronavirus disease (COVID-19). The aim of the study was to describe the extent and the impacts of 2021 COVID-19 outbreaks on LTCFs in Taiwan. METHODS: We retrospectively analyzed the data of each COVID-19 outbreak in LTCFs from May 15 to July 31, 2021 in Taiwan. We characterized the features of LTCFs with outbreaks and compared the characteristics of infected staff members and residents of the affected LTCFs. RESULTS: COVID-19 outbreaks were reported in 16 LTCFs (0.9%). The outbreak was significantly associated with LTCFs with ≥50 beds [adjusted odds ratio (aOR), 6.3; 95%confidence interval [CI], 1.9-21.1] and location of Taipei metropolitan area (aOR, 4.6; 95%CI, 1.7-12.8). Resident cases accounted for 75.4% (203/269) of confirmed cases affected by outbreaks. The 30-day all-cause mortality was 24.2% for residents only and was significantly associated with age ≥65 years [adjusted hazard ratio (aHR, 4.3; 95%CI, 1.7-10.5)], presence of symptoms on diagnosis (aHR, 2.2; 95%CI, 1.3-3.7), and LTCF occupancy rate ≥80% (aHR, 3.0, 95%CI, 1.3-7.4). CONCLUSION: COVID-19 outbreaks have a critical impact on residents in LTCFs owing to the advanced age and high prevalence of chronic comorbidities in this population. Multi-pronged infection control measures and mass testing are vital for mitigating COVID-19 transmission in LTCFs.

Chlorhexidine Bathing to Prevent Central Line-Associated Bloodstream Infections in Hematology Units: A Prospective, Controlled Cohort Study.

BACKGROUND: Chlorhexidine (CHG) bathing decreases the incidence of bloodstream infections in intensive care units, but its effect has been understudied in patients with hematological malignancies in noncritical care units. METHODS: Adults with hematological malignancies hospitalized for cytotoxic chemotherapy in noncritical care units were offered daily 2% CHG bathing. We compared outcomes of patients who chose CHG bathing (CHG group) with outcomes of those who did not choose CHG bathing (usual-care group). The primary outcome was gram-positive cocci-related, skin flora-related, or central line-associated bloodstream infection. The negative control outcome was gut-origin bacteremia. RESULTS: The CHG group (n = 485) had a crude incidence rate of the primary outcome that was 60% lower than the rate for the usual-care group (n = 408; 3.4 vs 8.4 per 1000 patient-days, P = .02) but had a similar crude incidence rate of the negative control outcome (4.5 vs 3.2 per 1000 patient-days; P = .10). In multivariable analyses, CHG bathing was associated with a 60% decrease in the primary outcome (adjusted hazard ratio [HR], 0.4; P < .001). In contrast, CHG bathing had no effect on the negative control outcome (adjusted HR, 1.1; P = .781). CHG bathing was well tolerated by participants in the CHG group. CONCLUSIONS: CHG bathing could be a highly effective approach for preventing gram-positive cocci-related, skin flora-related, or central line-associated bacteremia in patients with hematological malignancies who are hospitalized for cytotoxic chemotherapy in noncritical care units.

A No-Notice Drill of Hospital Preparedness in Responding to Ebola Virus Disease in Taiwan.

The Ebola virus was first discovered in 1976, but the outbreak of Ebola virus disease that began in Guinea, West Africa, in December 2013 shocked the world. It is the largest and most severe epidemic of Ebola virus disease to date. The US Centers for Disease Control and Prevention confirmed that inadequate implementation of the policy of acquiring travel history led to a delay in identifying the first imported Ebola virus disease case. The Taiwan Centers for Disease Control developed a no-notice drill that used a simulated patient to assess hospitals' emergency preparedness capacity in responding to Ebola virus disease. Despite the fact that regular inspection shows that more than 90% of regional hospitals and medical centers inquired about patients' travel history, occupation, contact history, and cluster information, the no-notice drill revealed that more than 40% of regional hospitals and medical centers failed to ask emergency room patients about these factors. Therefore, to assist in inquiries about travel history, occupation, contact history, and cluster information in emergency triage and outpatient settings, the Taiwan CDC revised the criteria for hospital infection control inspection. It requested that hospitals issue appropriate reminders and implement process control mechanisms to block diagnostic processes in instances in which healthcare workers do not inquire about travel history, occupation, contact history, and cluster information. Furthermore, the Taiwan CDC will continue no-notice inspections in order to strengthen hospitals' infection control measures and reduce the risk of infectious disease transmission in the healthcare system.

Excess mortality and long-term disability from healthcare-associated staphylococcus aureus infections: a population-based matched cohort study.

BACKGROUND: Staphylococcus aureus is a leading cause of healthcare-associated infections (HAIs), but the impact of S. aureus HAIs on the long-term survival and functional status of hospitalized patients remain unknown. This study aimed to examine whether S. aureus HAIs increase the risks for long-term mortality and disability. METHODS: We conducted a retrospective population-based matched cohort study of inpatients at 8 medical centers, 43 regional hospitals, and 63 local hospitals which participated in the Taiwan Nosocomial Infection Surveillance (TNIS). We individually matched 3070 patients with S. aureus HAIs to 6140 inpatients without HAIs at a 1∶2 ratio by age, gender, hospital, specialty, underlying diseases, and the length of stay before onset of the S. aureus HAI. Main outcome measures are one-year excess risks for mortality, new-onset chronic ventilator dependence, and new-onset dialysis-dependent end-stage renal disease. RESULTS: We found that patients with S. aureus HAIs had an excess one-year mortality of 20.2% compared with matched uninfected inpatients (P<0.001). The excess risk for new-onset chronic ventilator dependence and dialysis-dependent end-stage renal disease was 7.3% and 2.6%, respectively (Ps<0.001). S. aureus HAIs were also associated with an excess hospital stay of 12 days and an extra cost of $5978 (Ps<0.001). CONCLUSION: S. aureus HAIs have substantial negative effect on the long-term outcome of hospitalized patients in terms of both mortality and disability, which should be taken into consideration in future cost-effectiveness studies of the control and prevention interventions for S. aureus HAIs.

Increase of carbapenem-resistant Acinetobacter baumannii infection in acute care hospitals in Taiwan: association with hospital antimicrobial usage.

OBJECTIVE: Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as an important pathogen causing healthcare-associated infections (HAIs) in Taiwan. The present study is aimed to investigate the epidemiology of HAIs caused by CRAB and the association of CRAB infection and hospital usage of different antimicrobials. METHODS: Two nationwide databases in the period 2003 to 2008, the Taiwan Nosocomial Infection Surveillance System and National Health Insurance claim data, were used for analysis. A total of 13,811 healthcare-associated A. baumannii infections and antimicrobial usage data from 121 hospitals were analyzed. RESULTS: There was a significant increase in the proportion of number of HAIs caused by CRAB over that by all A. baumannii (CRABpAB), from 14% in 2003 to 46% in 2008 (P<0.0001). The greatest increase was in central Taiwan, from 4% in 2003 to 62% in 2008 (P<0.0001). Use of anti-pseudomonal carbapenems, but not other classes of antibiotics, was significantly correlated with the increase of CRABpAB (r = 0.86, P<0.0001). CONCLUSIONS: We suggested that dedicated use of anti-pseudomonal carbapenems would be an important intervention to control the increase of CRABpAB.

Comparative analysis of full genomic sequences among different genotypes of dengue virus type 3.

BACKGROUND: Although the previous study demonstrated the envelope protein of dengue viruses is under purifying selection pressure, little is known about the genetic differences of full-length viral genomes of DENV-3. In our study, complete genomic sequencing of DENV-3 strains collected from different geographical locations and isolation years were determined and the sequence diversity as well as selection pressure sites in the DENV genome other than within the E gene were also analyzed. RESULTS: Using maximum likelihood and Bayesian approaches, our phylogenetic analysis revealed that the Taiwan's indigenous DENV-3 isolated from 1994 and 1998 dengue/DHF epidemics and one 1999 sporadic case were of the three different genotypes - I, II, and III, each associated with DENV-3 circulating in Indonesia, Thailand and Sri Lanka, respectively. Sequence diversity and selection pressure of different genomic regions among DENV-3 different genotypes was further examined to understand the global DENV-3 evolution. The highest nucleotide sequence diversity among the fully sequenced DENV-3 strains was found in the nonstructural protein 2A (mean +/- SD: 5.84 +/- 0.54) and envelope protein gene regions (mean +/- SD: 5.04 +/- 0.32). Further analysis found that positive selection pressure of DENV-3 may occur in the non-structural protein 1 gene region and the positive selection site was detected at position 178 of the NS1 gene. CONCLUSION: Our study confirmed that the envelope protein is under purifying selection pressure although it presented higher sequence diversity. The detection of positive selection pressure in the non-structural protein along genotype II indicated that DENV-3 originated from Southeast Asia needs to monitor the emergence of DENV strains with epidemic potential for better epidemic prevention and vaccine development.

Retrospective serological study on sequential dengue virus serotypes 1 to 4 epidemics in Tainan City, Taiwan, 1994 to 2000.

BACKGROUND AND PURPOSE: We previously reported the development of a non-structural protein NS1 serotype-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) for dengue serodiagnosis and seroepidemiological study. This assay can be used to differentiate the immunologic status of individuals into naive, primary, or secondary dengue virus (DENV) infection and identify the DENV serotypes of primary infection. A retrospective study was conducted to investigate the serological responses of confirmed dengue cases infected during each of the sequential DENV-1 (August 1994 to February 1995), DENV-2 (August to December 1997), DENV-3 (August 1998 to January 1999), and DENV-4 (June to December 2000) epidemics in Tainan City, Taiwan. METHODS: 218 serum samples collected 1.1 to 7.2 years postinfection were analyzed by NS1 serotype-specific IgG ELISA together with corresponding acute and/or convalescent serum samples when available. The immunological status and the infecting DENV serotypes were determined for these individuals. RESULTS: High titers of dengue NS1 serotype-specific IgG antibody could be detected in serum samples. Differentiation of immunological status showed that 76.6% and 23.4% of cases had primary and secondary infections, respectively. A significant age-dependent increase in the rate of secondary infection was observed for those cases born before 1942. Notably, analysis of postinfection serum samples of 17 dengue hemorrhagic fever patients infected during the 1998 DENV-3 epidemic showed that 9 cases (53%) had primary infections. CONCLUSIONS: Our data revealed that a majority of the population born after 1943 in Tainan City are naive to DENV infection and are at high risk of infection with all 4 DENV serotypes.

Laboratory-based dengue surveillance in Taiwan, 2005: a molecular epidemiologic study.

We present the results of laboratory-based dengue surveillance in Taiwan for 2005. A phylogenetic study showed that multiple dengue epidemics were caused by three different imported dengue virus (DENV) strains. A strain of DENV-3 (genotype I) imported from the Philippines first appeared in the southern part of Kaohsiung City and later spread to Kaohsiung County from August to December, which resulted in 77 cases of dengue. Another strain of DENV-3 (genotype II) imported from Vietnam first appeared in the central part of Kaohsiung City and later spread to Kaohsiung County from September to December, which resulted in 35 cases of dengue. A strain of DENV-2 (American/Asian genotype) imported from Vietnam first appeared in Tainan City and later spread to Kaohsiung City/County from October to December, which resulted in 60 cases of dengue. This study provides molecular epidemiologic evidence that most dengue in Taiwan is caused by imported strains of the virus.

Development of real-time reverse transcriptase PCR assays to detect and serotype dengue viruses.

Serotyping dengue virus (DENV) from suspect human specimens is crucial for developing sound epidemiological control measurements early in the transmission season and for effective patient management. We modified DENV consensus D1 (mD1) and serotype-specific TS2 (mTS2) and redesigned serotype-specific TS1 (rTS1) and TS4 (rTS4) as described previously in the conventional capsid and premembrane gene (C-prM) protocol (R. S. Lanciotti, C. H. Calisher, D. J. Gubler, G.-J. Chang, A. V. Vorndam, J. Clin. Microbiol. 30:545-551, 1992). In addition, we designed two new sets of amplimers and probes, located at nonstructural protein 5 (NS5) and the 3' noncoding region (3'NC) of DENV. The NS5 protocol utilizes two flaviviral consensus outer amplimers (mFU1 and CFD2) and four dengue virus serotype-specific TaqMan fluorogenic probes. The 3'NC protocol uses two DENV consensus amplimers, DC10418 and CDC10564. The conventional gel-based, heminested detection method was adapted for the C-prM protocol for detecting and serotyping dengue viruses. In addition, we developed the real-time SYBR green I and postamplification melting temperature curve analysis for the mD1/TS and 3'NC protocols using identical amplification conditions. The NS5 amplimer/probe set was formulated as a one-tube, multiplex, real-time reverse transcriptase PCR for serotype identification. Three sets of amplimers and probes were verified for their specificity in tests with yellow fever, Japanese encephalitis, St. Louis encephalitis, and West Nile viruses; optimized against 109 DENV strains; and validated for detection of the virus in sera from two different panels of acute-phase human dengue serum specimens and one panel of virus isolates from dengue patients' serum specimens. Clinical evaluation by two separate laboratories indicated that the C-prM was more sensitive (100%) than the NS5 (91%) or the 3'NC (91%) protocol.

Fever screening at airports and imported dengue.

Airport fever screening in Taiwan, July 2003-June 2004, identified 40 confirmed dengue cases. Results obtained by capture immunoglobulin (Ig) M and IgG enzyme-linked immunoassay, real time 1-step polymerase chain reaction, and virus isolation showed that 33 (82.5%) of 40 patients were viremic. Airport fever screening can thus quickly identify imported dengue cases.

Dengue virus serotyping based on envelope and membrane and nonstructural protein NS1 serotype-specific capture immunoglobulin M enzyme-linked immunosorbent assays.

Envelope and membrane (E/M) and nonstructural protein NS1 serotype-specific capture Immunoglobulin M (IgM) enzyme-linked immunosorbent assays (ELISAs) were developed to differentiate four dengue virus serotypes. A total of 93 anti-dengue virus IgM-positive serum samples collected between days 5 and 45 of illness from 59 confirmed dengue patients were analyzed. The results showed that positive serotype specificity could be identified for 86.1 and 47.6% of serum samples tested for E/M-specific IgM antibodies versus 83.3 and 42.9% of serum samples tested for NS1-specific IgM antibodies from patients with primary and secondary dengue virus infections, respectively. Dual analyses with both E/M and NS1 serotype-specific capture IgM ELISAs showed that positive serotype specificity could be correctly identified for 98.6 and 61.9% of all of the primary and secondary serum samples tested, respectively. These findings suggested that E/M and NS1 serotype-specific capture IgM ELISAs have the potential to be of use in dengue virus serotyping.

Comparison of capture immunoglobulin M (IgM) and IgG enzyme-linked immunosorbent assay (ELISA) and nonstructural protein NS1 serotype-specific IgG ELISA for differentiation of primary and secondary dengue virus infections.

We have found that NS1 serotype-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) can be used to differentiate primary and secondary dengue virus infections. This is due to the fact that the NS1-specific IgG antibody cannot be detected before day 9 of illness for primary infection, so the NS1-specific IgG antibodies measured in acute-phase sera must come from previous infection. Comparison of NS1 serotype-specific IgG ELISA with envelope- and membrane-specific capture IgM and IgG ELISA in the differentiation of primary and secondary dengue virus infections showed good correlation (95.90% agreement). Most important, we have found that the serotype of the dengue virus from the majority of patients with primary infection could be correctly identified when convalescent-phase or postinfection sera were analyzed by NS1 serotype-specific IgG ELISA. These findings suggested that NS1 serotype-specific IgG ELISA could be reliably applied for serodiagnosis and seroepidemiological study of dengue virus infection.

Development of group- and serotype-specific one-step SYBR green I-based real-time reverse transcription-PCR assay for dengue virus.

A quantitative one-step SYBR Green I-based reverse transcription (RT)-PCR system was developed for the detection and differentiation of four different dengue virus serotypes in acute-phase serum samples. A set of group- and serotype-specific primer pairs was designed against conserved sequences in the core region and evaluated for clinical diagnosis. A linear relationship was obtained between the amount of input RNA and cycle threshold (Ct) value over a range of 10 to 10(7) PFU per ml of cell culture-derived dengue viruses. The detection limit of the group-specific primer pair was between 4.1 and 43.5 PFU/ml for four dengue serotypes. The detection limit of each of the serotype-specific primer pairs was calculated to be 10 PFU/ml for dengue virus serotype 1 (DEN-1), 4.6 PFU/ml for DEN-2, 4.1 PFU/ml for DEN-3, and 5 PFU/ml for DEN-4. Comparisons between the one-step SYBR Green-based RT-PCR assay and the conventional cell culture method in the clinical diagnosis of dengue virus infection from acute-phase serum samples of confirmed dengue patients were performed. The results showed that 83 and 67% of 193 acute-phase serum samples tested were positive by the one-step SYBR Green-based RT-PCR method and cell culture method, respectively. Further analysis showed that the one-step SYBR Green-based RT-PCR method could detect twice as many acute-phase serum samples with positive dengue-specific immunoglobulin M (IgM) and/or IgG antibodies than cell culture method. Our results demonstrate the potential clinical application of the one-step SYBR Green I-based RT-PCR assay for the detection and differentiation of dengue virus RNA.