Assessment of the Risk of Severe Dengue Using Intrahost Viral Population in Dengue Virus Serotype 2 Patients via Machine Learning.

Dengue virus, a positive-sense single-stranded RNA virus, continuously threatens human health. Although several criteria for evaluation of severe dengue have been recently established, the ability to prognose the risk of severe outcomes for dengue patients remains limited. Mutant spectra of RNA viruses, including single nucleotide variants (SNVs) and defective virus genomes (DVGs), contribute to viral virulence and growth. Here, we determine the potency of intrahost viral population in dengue patients with primary infection that progresses into severe dengue. A total of 65 dengue virus serotype 2 infected patients in primary infection including 17 severe cases were enrolled. We utilized deep sequencing to directly define the frequency of SNVs and detection times of DVGs in sera of dengue patients and analyzed their associations with severe dengue. Among the detected SNVs and DVGs, the frequencies of 9 SNVs and the detection time of 1 DVG exhibited statistically significant differences between patients with dengue fever and those with severe dengue. By utilizing the detected frequencies/times of the selected SNVs/DVG as features, the machine learning model showed high average with a value of area under the receiver operating characteristic curve (AUROC, 0.966 ± 0.064). The elevation of the frequency of SNVs at E (nucleotide position 995 and 2216), NS2A (nucleotide position 4105), NS3 (nucleotide position 4536, 4606), and NS5 protein (nucleotide position 7643 and 10067) and the detection times of the selected DVG that had a deletion junction in the E protein region (nucleotide positions of the junction: between 969 and 1022) increased the possibility of dengue patients for severe dengue. In summary, we demonstrated the detected frequencies/times of SNVs/DVG in dengue patients associated with severe disease and successfully utilized them to discriminate severe patients using machine learning algorithm. The identified SNVs and DVGs that are associated with severe dengue will expand our understanding of intrahost viral population in dengue pathogenesis.

Multicenter evaluation of two chemiluminescence and three lateral flow immunoassays for the diagnosis of COVID-19 and assessment of antibody dynamic responses to SARS-CoV-2 in Taiwan.

This multicenter, retrospective study included 346 serum samples from 74 patients with coronavirus disease 2019 (COVID-19) and 194 serum samples from non-COVID-19 patients to evaluate the performance of five anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests, i.e. two chemiluminescence immunoassays (CLIAs): Roche Elecsys® Anti-SARS-CoV-2 Test (Roche Test) and Abbott SARS-CoV-2 IgG (Abbott Test), and three lateral flow immunoassays (LFIAs): Wondfo SARS-CoV-2 Antibody Test (Wondfo Test), ASK COVID-19 IgG/IgM Rapid Test (ASK Test), and Dynamiker 2019-nCoV IgG/IgM Rapid Test (Dynamiker Test). We found high diagnostic sensitivities (%, 95% confidence interval [CI]) for the Roche Test (97.4%, 93.4-99.0%), Abbott Test (94.0%, 89.1-96.8%), Wondfo Test (91.4%, 85.8-94.9%), ASK Test (97.4%, 93.4-99.0%), and Dynamiker Test (90.1%, 84.3-94.0%) after >21 days of symptom onset. Meanwhile, the diagnostic specificity was 99.0% (95% CI, 96.3-99.7%) for the Roche Test, 97.9% (95% CI, 94.8-99.2%) for the Abbott Test, and 100.0% (95% CI, 98.1-100.0%) for the three LFIAs. Cross-reactivity was observed in sera containing anti-cytomegalovirus (CMV) IgG/IgM antibodies and autoantibodies. No difference was observed in the time to seroconversion detection of the five serological tests. Specimens from patients with COVID-19 pneumonia demonstrated a shorter seroconversion time and higher chemiluminescent signal than those without pneumonia. Our data suggested that understanding the dynamic antibody response after COVID-19 infection and performance characteristics of different serological test are crucial for the appropriate interpretation of serological test result for the diagnosis and risk assessment of patient with COVID-19 infection.

Global epidemiology of coronavirus disease 2019 (COVID-19): disease incidence, daily cumulative index, mortality, and their association with country healthcare resources and economic status.

It has been 2 months since the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. So far, COVID-19 has affected 85 403 patients in 57 countries/territories and has caused 2924 deaths in 9 countries. However, epidemiological data differ between countries. Although China had higher morbidity and mortality than other sites, the number of new daily cases in China has been lower than outside of China since 26 February 2020. The incidence ranged from 61.44 per 1 000 000 people in the Republic of Korea to 0.0002 per 1 000 000 people in India. The daily cumulative index (DCI) of COVID-19 (cumulative cases/no. of days between the first reported case and 29 February 2020) was greatest in China (1320.85), followed by the Republic of Korea (78.78), Iran (43.11) and Italy (30.62). However, the DCIs in other countries/territories were <10 per day. Several effective measures including restricting travel from China, controlling the distribution of masks, extensive investigation of COVID-19 spread, and once-daily press conferences by the government to inform and educate people were aggressively conducted in Taiwan. This is probably the reason why there was only 39 cases (as of 29 February 2020) with a DCI of 1 case per day in Taiwan, which is much lower than that of nearby countries such as the Republic of Korea and Japan. In addition, the incidence and mortality were correlated with the DCI. However, further study and continued monitoring are needed to better understand the underlying mechanism of COVID-19.

Reduced economic burden of AIDS-defining illnesses associated with adherence to antiretroviral therapy.

OBJECTIVES: We assessed the economic burden of AIDS-defining illnesses (ADIs), which was further stratified by adherence to antiretroviral therapy (ART). METHODS AND MATERIALS: A nationwide longitudinal cohort of 18,234 incident cases with HIV followed for 11years was utilized. Adherence to ART was measured by medication possession ratio (MPR). Generalized estimating equations modeling was used to estimate the cost impact of ADIs. RESULTS: Having opportunistic infections increased the annual cost by 9% (varicella-zoster virus infection) to 98% (cytomegalovirus disease), while the annual costs increased by 26% (Kaposi's sarcoma) to 95% (non-Hodgkin's lymphoma) in the year when AIDS-related cancer occurred. ADIs occurred more frequently in the years with low adherence for ART compared to the high-adherence years (e.g., 0.1≤MPR<0.8 vs. MPR≥0.8, event rate of cytomegalovirus disease 4.03% vs. 0.51%). The annual baseline costs in the years with MPR<0.1, 0.1≤MPR<0.8, and MPR≥0.8 were $250, $4,752, and $8,990 (in 2018 USD), respectively. The economic impact of ADIs in the years with low adherence (MPR<0.1) was larger than that in the high-adherence years (MPR≥0.8) (e.g., MPR<0.1 vs. MPR≥0.8, annual cost increased by 244% vs. 9% when candidiasis occurred). CONCLUSIONS: Adherence to ART may increase the baseline medical costs but mitigate the incidence and economic burden of ADIs.

Clinical benefits of antimicrobial de-escalation in adults with community-onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis bacteremia.

The clinical benefits of an antimicrobial de-escalation strategy were compared with those of a no-switch strategy in bacteremic patients. Adults with community-onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis bacteremia treated empirically using broad-spectrum beta-lactams, including third-generation cephalosporins (GCs), fourth-GC or carbapenems, were treated definitively with first- or second-GCs (de-escalation group), the same regimens as empirical antibiotics (no-switch group), or antibiotics with a broader-spectrum than empirical antibiotics (escalation group). The eligible 454 adults were categorized as the de-escalation (231 patients, 50.9%), no-switch (177, 39.0%), and escalation (46, 10.1%) groups. Patients with de-escalation therapy were more often female, had less critical illness and fatal comorbidity, and had a higher survival rate than patients in the other two groups. After propensity score matching in the de-escalation and no-switch groups, critical illness at onset (Pitt bacteremia score ≥ 4; 16.5% vs. 12.7%; P = 0.34) or day 3 (2.5% vs. 2.5%; P = 1.00), fatal comorbidity (16.5% vs. 21.5%; P = 0.25), time to defervescence (4.6 vs. 4.7 days; P = 0.89), hospital stays (11.5 vs. 10.3 days; P = 0.13) and 4-week crude mortality rate (4.4% vs. 4.4%; P = 1.00) were similar. However, lower antibiotic cost (mean: 212.1 vs. 395.6 US$, P <0.001) and fewer complications of bloodstream infections due to resistant pathogens (0% vs. 5.1%, P = 0.004) were observed in the de-escalation group. De-escalation to narrower-spectrum cephalosporins is safe and cost-effective for adults with community-onset EKP bacteremia stabilized by empirical broad-spectrum beta-lactams.

Incidence of Neurological Disorders Among HIV-Infected Individuals With Universal Health Care in Taiwan From 2000 to 2010.

OBJECTIVE: To determine the incidence of and factors associated with neurological disorders in a large Taiwanese cohort of HIV-infected persons with free access to highly active antiretroviral therapy (HAART). DESIGN: A retrospective population-based cohort study was conducted using the National Health Insurance Research Database for the years 2000-2010. METHODS: We identified 13,316 HIV-positive persons from 2000 through 2010. We used direct standardization to calculate age-adjusted and sex-adjusted incidence rates based on the 2000 World Health Organization world standard population. Factors associated with neurological disorders were analyzed using a Cox proportional hazards model. RESULTS: The standardized incidence of neurological disorders among HIV-infected persons increased from 22.16 per 1000 person-years in 2000 to 25.23 per 1000 person-years in 2010. Cognitive disorders increased significantly from 0.36 per 1000 person-years in 2001 to 7.44 per 1000 person-years in 2010 (trend P < 0.001). The rate of neurological disorders increased with age ≥55 years [adjusted hazard ratios (AHRs) 2.54, 95% confidence interval (CI): 1.89 to 3.40], hypertension (AHR 1.41, 95% CI: 1.12 to 1.76), substance abuse (AHR 1.65, 95% CI: 1.36 to 2.02), opportunistic infection (AHR 1.76, 95% CI: 1.47 to 2.11), syphilis (AHR 1.27, 95% CI: 1.10 to 1.47), and emergency department visits >5 (AHR 2.41, 95% CI: 1.96 to 2.97). The incidence of neurological disorders was negatively associated with adherence to HAART (adherence ≥85% AHR: 0.79, 95% CI: 0.64 to 0.97). CONCLUSIONS: The rising incidence of cognitive disorders among HIV-positive persons highlights the need to provide routine neurological evaluations at clinical visits. Receiving HAART with adherence ≥85% contributes to a reduced risk of neurological disorders.

Case management interventions for HIV-infected individuals.

Engagement of HIV-positive persons into care and achieving optimal antiretroviral treatment outcomes is a fundamental HIV prevention strategy. Case management model was recommended as a beneficial model of care for patients with a new HIV diagnosis, focusing on individuals with unmet needs, and linking them with the coordinated health and social services to achieve desired outcomes. HIV case management is population-driven and programs are designed to respond to the unique needs of the client population they serve, such as substance users, homeless, youth, and prison inmates. This view found 28 studies addressing effectiveness and impacts of case management intervention for people living with or at risk of HIV/AIDS. Effectiveness of case management intervention was categorized as follows: decreased mortality and improve health outcomes, linkage to and retention in care, decreased unmet needs, and reducing risky behaviors.

Agreement assessment of tigecycline susceptibilities determined by the disk diffusion and broth microdilution methods among commonly encountered resistant bacterial isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2008 to 2010.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor the in vitro activity of tigecycline against commonly encountered drug-resistant bacteria. This study compared the in vitro activity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistant Staphylococcus aureus (MRSA; n = 759), vancomycin-resistant Enterococcus faecium (VRE; n = 191), extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (n = 602), ESBL-producing Klebsiella pneumoniae (n = 736), and Acinetobacter baumannii (n = 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC(90) values of tigecycline against MRSA, VRE, ESBL-producing E. coli, ESBL-producing K. pneumoniae, and A. baumannii were 0.5, 0.125, 0.5, 2, and 8 µg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producing K. pneumoniae and 33.8% for A. baumannii. Using the EUCAST criteria, the total error rate was also high (54.6%) for A. baumannii isolates. The total error rates between these two methods were <5% for MRSA, VRE, and ESBL-producing E. coli. For routine susceptibility testing of ESBL-producing K. pneumoniae and A. baumannii against tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.

One-year follow-up of relapse to risky behaviors and incidence of syphilis among patients enrolled in the HIV case management program.

A longitudinal prospective study was conducted at an AIDS designated hospital in Taiwan. The study aimed to determine the incidence of syphilis and to identify risk factors predicting new onset syphilis and relapse into risky behaviors among 117 patients enrolled in the HIV case management program for 1 year. Having a new episode of syphilis was defined as patients had a fourfold increase of serum rapid plasma reagin titers from baseline to 12-month follow-up. After enrollment, 17% relapsed in unprotected sexual intercourse. New onset syphilis was noted in ten (10.4%) participants, and all were men having sex with men. The incidence of syphilis was 5.8 per 100 person-years. Predictors of a new episode of syphilis were higher CD4 cell counts [hazard ratio (HR), 1.003; 95% confidence interval (CI), 1.00-1.006], and recreational drug use (HR, 18.89; 95% CI, 2.78-128.15). Regular screening for syphilis among patients retaining in HIV care remains necessary.

Clinical and economic impact of multidrug resistance in nosocomial Acinetobacter baumannii bacteremia.

OBJECTIVE: To investigate the impact of antimicrobial resistance on clinical and economic outcomes among hospitalized patients with multidrug-resistant (MDR) Acinetobacter baumannii bacteremia. DESIGN: A retrospective, matched-cohort study. SETTING: A tertiary care university teaching hospital. METHODS: A matched case-control (1 : 1) study was conducted to compare the differences in clinical and economic outcomes of patients with MDR A. baumannii bacteremia and patients with non-MDR A. baumannii bacteremia. Case patients were matched to control patients on the basis of sex, age, severity of underlying and acute illness, and length of hospital stay before onset of bacteremia. RESULTS: Forty-six (95.8%) of 48 cases with MDR A. baumannii bacteremia were eligible for the study and matched with appropriate controls. The sepsis-related mortality rate was 34.8% among cases and 13.0% among controls, for an attributable mortality rate of 21.8% (adjusted odds ratio, 4.1 [95% confidence interval, 1.1-15.7]; P=.036). After the onset of bacteremia, cases and controls had a significantly different length of hospital stay (54.2 vs 34.1 days; P=.006), hospitalization cost (US$9,349 vs US$4,865; P=.001), and antibiotic therapy cost (US$2,257 vs US$1,610; P=.014). Thus, bacteremia due to MDR A. baumannii resulted in 13.4 days of additional hospitalization and US$3,758 of additional costs, compared with bacteremia due to non-MDR A. baumannii. CONCLUSIONS: Patients with MDR A. baumannii bacteremia had a higher mortality rate and incurred greater medical costs than patients with non-MDR A. baumannii bacteremia.