Jui-Kuang Chen

High prevalence of latent tuberculosis infection in dialysis patients using the interferon-{gamma} release assay and tuberculin skin test

BACKGROUND AND OBJECTIVES Patients in ESRD on hemodialysis with latent tuberculosis (TB) infection have 10 to 25 times the risk of reactivation into active disease compared with healthy adults. This study investigates the prevalence of latent TB infection in dialysis patients from a country with an intermediate burden of TB and its associated risk factors using the QuantiFERON-TB Gold in-tube test (QGIT) and the tuberculin skin test (TST). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a prospective, cross-sectional study performed at a medical center in Taiwan on dialysis patients. Each patient underwent QGIT, two-step TST using 2 tuberculin units (TU) of PPD RT-23, a chest x-ray to exclude active TB, and an interview to determine TB risk factors. RESULTS Ninety-three of 190 eligible patients were enrolled: 35 men and 58 women. 64.8% were vaccinated with the Bacille-Calmette-Guérin (BCG) vaccination. Overall, 34.4% were positive by QGIT and 10.8% were indeterminate. Using a 10-mm TST cutoff, 53.9% were positive. There was poor correlation between TST and QGIT at any TST cutoff criteria. There was a significant increasing trend of QGIT positivity with age in those younger than 70 years, and, conversely, a decreasing trend of TST reactivity with age. Significant risk factors for QGIT positivity included age and past TB disease. CONCLUSIONS This study shows a high prevalence of latent TB infection in dialysis patients in a country with an intermediate burden of TB. QGIT in dialysis patients correlated better than TST with the risk of TB infection and past TB disease.

Prevalence of latent tuberculosis infection in BCG-vaccinated healthcare workers by using an interferon-gamma release assay and the tuberculin skin test in an intermediate tuberculosis burden country

BACKGROUND The risk of healthcare workers (HCWs) acquiring tuberculosis (TB) infection is high. We determined the prevalence of latent TB infection (LTBI) in HCWs with a high Bacille Calmette-Guérin (BCG) vaccine coverage in an intermediate TB burden country by using an interferon-gamma release assay [QuantiFERON-TB Gold (QFT-G)] and by using the tuberculin skin test (TST). Risk factors associated with a positive test were determined. METHODS This prospective cross-sectional study enrolled HCWs from a medical center in Taiwan. Participants were grouped into workers without exposure (Group 1) and workers who self-reported a history of TB exposure (Group 2). All participants completed a questionnaire to collect demographic information and risk factors for acquiring TB. The QFT-G test and the TST were administered and risk factors for a positive test were analyzed. RESULTS We recruited 193 HCWs [149 (77.2%) female workers] with a mean age of 35.6 years. All were BCG-vaccinated. The prevalence of LTBI was 88.8% (based on the TST) and 14.5% (based on the QFT-G test). There was no difference between HCWs with and without known exposure to TB. Agreement between the tests was poor (i.e., the kappa value was less than 0.05). Multivariable logistic regression showed that only the QFT-G test was associated with age (35 years or greater) (adjusted OR, 2.53; p = 0.03). CONCLUSION By using the QFT-G test or TST, this study found a similar prevalence of LTBI in HCWs with and without known exposure to TB. This suggests that in intermediate TB burden countries exposure to TB may occur within the hospital and within the community. Compared to the TST, the QFT-G test was correlated better with age, which is a known risk factor for latent TB infection.

Non-nosocomial healthcare-associated infective endocarditis in Taiwan: an underrecognized disease with poor outcome

BackgroundNon-nosocomial healthcare-associated infective endocarditis (NNHCA-IE) is a new category of IE of increasing importance. This study described the clinical and microbiological characteristics and outcome of NNHCA-IE in Taiwan.MethodsA retrospective study was conducted of all patients with IE admitted to the Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan over a five-year period from July 2004 to July 2009. The clinical and microbiological features of NNHCA-IE were compared to those of community-acquired and nosocomial IE. Predictors for in-hospital death were determined.ResultsTwo-hundred episodes of confirmed IE occurred during the study period. These included 148 (74%) community-acquired, 30 (15%) non-nosocomial healthcare-associated, and 22 (11%) nosocomial healthcare-associated IE. Staphylococcus aureus was the most frequent pathogen. Patients with NNHCA-IE compared to community-acquired IE, were older (median age, 67 vs. 44, years, p < 0.001), had more MRSA (43.3% vs. 9.5%, p < 0.001), more comorbidity conditions (median Charlson comorbidity index [interquartile range], 4[2-6] vs. 0[0-1], p < 0.001), a higher in-hospital mortality (50.0% vs. 17.6%, p < 0.001) and were less frequently recognized by clinicians on admission (16.7% vs. 47.7%, p = 0.002). The overall in-hospital mortality rate for all patients with IE was 25%. Shock was the strongest risk factor for in-hospital death (odds ratio 7.8, 95% confidence interval 2.4-25.2, p < 0.001).ConclusionsNNHCA-IE is underrecognized and carries a high mortality rate. Early recognition is crucial to provide optimal management and improve outcome.

Higher rate of hepatitis events in patients with human immunodeficiency virus, hepatitis B, and hepatitis D genotype II infection: A cohort study in a medical center in southern Taiwan

BACKGROUND The epidemiology and impact of hepatitis δ virus (HDV) on hepatic outcomes and virological and immunological responses to highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) patients coinfected with hepatitis B virus (HBV) in northern Taiwan have been reported. However, the epidemiology and impact of HDV infection in HIV-HBV coinfection patients in southern Taiwan remains uncertain. METHODS In this cohort study, a total of 64 HIV patients coinfected with HBV were identified between January 1, 2009 and May 30, 2012. The seroprevalence of anti-HDV antibodies, HDV genotyping, clinical manifestations and hepatic outcomes were compared between the patients with and without HDV coinfection, and laboratory examinations and hepatic outcomes were recorded. RESULTS Among the 64 HIV patients coinfected with HBV, seven were seropositive for HDV (10.9%). There were no statistically significant differences in risk factors for acquiring HIV infection. During a median observation period of 27.8 months, the adjusted hazard ratio of HDV and HBV genotype (type B vs. non-type B) on hepatitis flare-ups were 62.132 (p = 0.04) and 0.028 (p = 0.01), respectively. All seven patients had genotype II and were HDV viremic. The phylogenetic tree analysis and clinical history evaluation did not identify any clusters of HDV infection. CONCLUSION HDV infection resulted in higher rate of hepatitis flare-ups, but it did not have a statistical significance on HIV progression and immunological response to HAART. Whether higher rate of HDV viremia has worse impact on the hepatic outcomes requires further investigation.

Prevalence and associated factors for HIV-1 transmitted drug resistance in voluntary clients for counseling and testing in Southern Taiwan

BACKGROUND According to the World Health Organization, HIV-transmitted drug resistance (TDR) is increasing. We analyzed voluntary counseling test data from a hospital in Southern Taiwan to investigate the TDR pattern in Southern Taiwan, the potential relationship between sexual behavior and HIV transmission, and HIV drug-resistant strain transmission. METHODS Genotypic resistance assays were performed on treatment-naïve HIV patients recruited from voluntary counseling testing (VCT) in Southern Taiwan from 2007 to 2011. Drug resistance-associated mutations were interpreted with Stanford University HIV Drug Resistance Database HIVdb program. Socio-demographics and sexual activity were recorded from the VCT questionnaire. Logistic regression analysis was used to analyze the risk factors for TDR, and a phylogenetic tree was constructed to elucidate the pattern of HIV drug-resistant strains. RESULTS Among the 161 treatment-naïve HIV-infected patients, most were men who reported having sex with men. The overall TDR rate was 10.6%. Patients with a history of sexually transmitted diseases had a 7.8-fold higher risk of becoming infected with genotypic resistant strains. CONCLUSION In Southern Taiwan, the HIV TDR rate was 10.6% among those receiving VCT. Our findings suggest that sexual behavior may play an important role in HIV drug-resistant strain transmission.

A nationwide covert observation study using a novel method for hand hygiene compliance in health care

HighlightsA novel covert observation method and reporting system was developed.The novel covert observation method is feasible for large‐scale observation.Overall hand hygiene compliance by covert observation is low in Taiwan.Hand hygiene compliance increases significantly with an increase in the number of indications within 1 hand hygiene opportunity. Background: Evaluation and feedback is a core hand hygiene (HH) improvement strategy. The covert observation method avoids observation bias inherent to the overt method. The aim of the study was to observe HH compliance by a novel covert method in a real‐world setting. Methods: We conducted a 2‐year, nationwide, prospective, observational study in teaching hospitals across Taiwan. Medical students and students who may have contact with patients in their careers were recruited as participants. A novel, shorthand notation method for covert observation was used. Observation results were reported through a study website. Results: There were a total of 25,379 HH opportunities covertly observed by 93 observers. Overall HH compliance was 32.0%. Health care workers had the highest HH compliance for indication 4 (42.6%), and the lowest for indication 5 (21.7%). Overall handrubbing percentage was high, reaching 83.6%. The HH compliance increased significantly with an increase in the number of indications within 1 HH opportunity (P < .001). Conclusions: The overall HH compliance by the covert observation method was low. An innovative shorthand notation method facilitated covert observation, and website reporting was demonstrated to be feasible for large‐scale observation.

High rate of HIV-1 drug resistance in treatment failure patients in Taiwan, 2009–2014

Background Drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) has been associated with loss of viral suppression measured by a rise in HIV-1 RNA levels, a decline in CD4 cell counts, persistence on a failing treatment regimen, and lack of adherence to combination antiretroviral therapy. Objectives This study aimed to monitor the prevalence and risk factors associated with drug resistance in Taiwan after failure of first-line therapy. Materials and methods Data from the Veterans General Hospital Surveillance and Monitor Network for the period 2009–2014 were analyzed. Plasma samples from patients diagnosed with virologic failure and an HIV-1 RNA viral load >1000 copies/mL were analyzed by the ViroSeq™ HIV-1 genotyping system for drug susceptibility. Hazard ratios (HRs) for drug resistance were calculated using a Cox proportional hazard model. Results From 2009 to 2014, 359 patients were tested for resistance. The median CD4 count and viral load (log) were 214 cells/μL (interquartile range [IQR]: 71–367) and 4.5 (IQR: 3.9–5.0), respectively. Subtype B HIV-1 strains were found in 90% of individuals. The resistance rate to any of the three classes of antiretroviral drugs (NRTI, NNRTI, and PI) was 75.5%. The percentage of NRTI, NNRTI, and PI resistance was 58.6%, 61.4%, and 11.4%, respectively. The risk factors for any class of drug resistance included age ≤35 years (adjusted HR: 2.30, CI: 1.48–3.56; p<0.0001), initial NNRTI-based antiretroviral regimens (adjusted HR: 1.70, CI: 1.10–2.63; p=0.018), and current NNRTI-based antiretroviral regimens when treatment failure occurs (odds ratio: 4.04, CI: 2.47–6.59; p<0.001). There was no association between HIV-1 subtype, viral load, and resistance. Conclusion This study demonstrated a high level of resistance to NRTI and NNRTI in patients with virologic failure to first-line antiretroviral therapy despite routine viral load monitoring. Educating younger men who have sex with men to maintain good adherence is crucial, as PI use is associated with lower possibility of drug resistance.

Elevated cerebrospinal fluid nitrite level in human immunodeficiency virus-infected patients with neurosyphilis

BACKGROUND/PURPOSE Human immunodeficiency virus (HIV) and syphilis coinfection is a common phenomenon. A percentage of neurosyphilis cases is asymptomatic in HIV-infected patients. The diagnosis of neurosyphilis is more difficult because of the alteration of cerebrospinal fluid (CSF) presentation by the HIV itself. The CSF levels of the degradation products of nitric oxide (NO; e.g., nitrate and nitrite) are reportedly elevated in animals and patients with bacterial meningitis. We hypothesized that an elevated CSF nitrite concentration may be present in patients coinfected with HIV and neurosyphilis. METHODS This cohort study was conducted from January 2007 to June 2008. Forty patients were enrolled and included seven patients in the control group and 33 HIV-infected patients with or without syphilis. Nitrite levels in the serum and the CSF were measured by using the Griess assay. RESULTS The CSF nitrite levels were significantly higher in HIV-infected patients with neurosyphilis, compared to the control group or patients with HIV infection only or patients with HIV and syphilis coinfection (p = 0.026). The CSF nitrite levels were correlated with the CSF white blood cell counts (Spearman correlation test, r(2) = 0.324; p < 0.001). There was no significant difference between different groups in serum nitrite levels. CONCLUSION Marked elevation of CSF nitrite level was observed in HIV-infected patients with neurosyphilis.

Rapid onset of rhabdomyolysis after switching to a raltegravir-based antiretroviral regimen

Raltegravir is the first integrase inhibitor antiretroviral agent that has been demonstrated to have antiviral efficacy and safety. However, the US Food and Drug Administration has recommended use with caution in patients with risk factors for rhabdomyolysis, based on four case reports of rhabdomyolysis in patients with identifiable risk factors. We present a 32-year-old Asian man with human immunodeficiency virus (HIV), but without other underlying diseases, who developed rapid-onset, raltegravir-associated rhabdomyolysis and hyperlactatemia. Our patient lacked predisposing factors for rhabdomyolysis, and the rapid onset time of 4 days was the shortest reported. Therefore, clinicians should exercise caution when using raltegravir and closely monitor all patients for the symptoms of muscle pain and weakness. This case has been reported to the National Adverse Drug Reactions Reporting System of the Department of Health in Taiwan.

HIV-1 integrase strand-transfer inhibitor resistance in southern Taiwan

The use of antiretroviral therapy has reduced rates of mortality and morbidity in patients with human immunodeficiency virus/acquired immune deficiency syndrome(HIV/AIDS). However, transmission of drug-resistant strains poses a challenge to control the spread of HIV-1. Primary resistance to integrase strand-transfer inhibitors (INSTIs) is rare despite their increased use. The prevalence of transmitted drug resistance (TDR) to INSTIs was 0.9% in northern Taiwan. This study was to analyse the prevalence and risk factors of TDR to INSTIs in southern Taiwan. In this study, we enrolled antiretroviral treatment-naïve HIV-1-infected subjects who underwent voluntary counselling and testing from 2013 to 2016 in southern Taiwan. Genotypic drug resistance, coreceptor tropism (CRT) and INSTI resistance were determined. Logistic regression was used to analyse the risk factors for INSTI polymorphic substitution. Sequences were obtained from 184 consecutive individuals, of whom 96.7% were men who have sex with men and 3.3% were heterosexual. Of the patients, 10% (19/183) had hepatitis B and 33.3% (61/183) had syphilis infection. Subtype B HIV-1 strains were found in 96.1% of the patients. Fifteen patients (8.4%, 15/178) harboured nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors or protease inhibitors resistance. CCR-5 coreceptors were used by 71.4% (130/184) of the patients. None of the patients had INSTI resistance-associated mutations, however 16 patients had INSTI polymorphic substitutions, and they were associated with a higher HIV viral load (p = 0.03, OR 2.4, CI 1.1–5.3) and syphilis infection (p = 0.03, OR 3.7, CI 1.1–12.0). In conclusion, no signature INSTI resistance-associated mutations were detected in our cohort. Continued monitoring of TDR to INSTI is needed due to the increased use of INSTIs.