Dengue virus (DENV) infection triggers the activation of autophagy to facilitate the viral replic... more Dengue virus (DENV) infection triggers the activation of autophagy to facilitate the viral replication cycle from various aspects. Although a number of stimulators are proposed to activate autophagy, none of them appears prior to the uncoating process. Given that T-cell immunoglobulin and mucin domain 1 (TIM-1) receptor is a putative DENV receptor and promotes apoptotic body clearance by autophagy induction, it raises the possibility that TIM-1 may participate in the activation of DENV-induced autophagy. In this study, confocal images first revealed the co-localization of TIM-1 with autophagosomes in DENV-induced autophagy rather than rapamycin-induced autophagy, suggesting the co-transportation of TIM-1 with DENV during infection. The treatment of siRNA to knockdown TIM-1 expression in DENV-infected GFP-microtubule-associated protein light chain 3 (LC3)-Huh7.5 cells revealed that TIM-1 is required not only for DENV cellular internalization but also for autophagy activation. Further...
Journal of Microbiology, Immunology and Infection, 2015
Patients with undetected bacteremia when discharged from a hospital are considered to have occult... more Patients with undetected bacteremia when discharged from a hospital are considered to have occult bacteremia. Klebsiella pneumoniae bacteremia (KPB) is endemic to Taiwan. Our purpose was to study the impact of occult KPB. We retrospectively reviewed the records of patients who were discharged from our emergency department (ED) and subsequently diagnosed with KPB (occult bacteremia), from January 2008 to March 2014. All patients are followed for at least 3 months after the index ED visit. The study group was compared to KPB patients who were directly hospitalized (DH) from ED in 2008. Thirty-day mortality was the primary endpoint. A total of 913 patients were admitted to our ED with KPB, and 88 of these patients (9.6%) had occult KPB. Among them, 43 had second ED visit and 41 were admitted. The overall 30-day mortality was 2.3%. Relative to patients with occult KPB, DH patients had more respiratory tract infections (p < 0.001) but fewer other intra-abdominal infections (p = 0.015). Liver abscess was the major diagnosis for the second ED visit (37.2%). DH patients had significantly greater 30-day mortality than that of overall patients with KPB (19.2% vs.2.3%, p < 0.001). Most patients with occult KPB had favorable outcomes, but about half of them required a second ED visit. Clinicians should aggressively follow patients with occult KPB and should seek to identify the focus of infection in this endemic area.
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi, Jan 31, 2015
Nontyphoid Salmonella (NTS) bacteremia causes high mortality and recurrence rates in human immuno... more Nontyphoid Salmonella (NTS) bacteremia causes high mortality and recurrence rates in human immunodeficiency virus (HIV)-infected patients. This study aimed to investigate the risk of recurrent NTS bacteremia in the era of combination antiretroviral therapy (cART). The medical records of consecutive HIV-infected patients with NTS bacteremia from January 2006 to June 2014 were reviewed. The patients were divided into two groups: patients who achieved a decline of plasma HIV RNA load by ≥ 2 log10 after 4 weeks of cART (good short-term virological response) and those who failed to achieve the goal (poor short-term virological response). Clinical information was collected on the demographics, immunological and virological responses, prophylactic antibiotics used, episodes of recurrent NTS bacteremia, and mortality. During the study period, 49 patients with 52 episodes of NTS bacteremia were included: 29 patients in the good virological response group, in which 16 received secondary proph...
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, Jan 8, 2015
Between 2010 and 2014, we obtained swab specimens to detect Treponema pallidum, with PCR assays, ... more Between 2010 and 2014, we obtained swab specimens to detect Treponema pallidum, with PCR assays, from the oral cavities of 240 patients with 267 episodes of syphilis who reported engaging in unprotected sex practices. The detected treponemal DNA was subjected to genotyping. All of the syphilis cases occurred in men who have sex with men (MSM), and 242 (90.6%) occurred in human immunodeficiency virus-infected patients. The stages of syphilis included 38 cases (14.2%) of primary syphilis of the genital region, 76 (28.5%) of secondary syphilis, 21 (7.9%) of primary and secondary syphilis, 125 (46.8%) of early latent syphilis, and seven (2.6%) others. Concurrent oral ulcers were identified in 22 cases (8.2%). Treponemal DNA was identified from the swabs of 113 patients (42.2%), including 15 (68.2%) with oral ulcers. The most common genotype of T. pallidum was 14f/f. The presence of oral ulcers was associated with identification of T. pallidum in the swab specimens (15/22 (68.2%) vs. 98/...
Diagnostic Microbiology and Infectious Disease, 2011
The purpose of this study was to investigate a cohort of patients with Burkholderia cepacia bacte... more The purpose of this study was to investigate a cohort of patients with Burkholderia cepacia bacteremia in the intensive care unit (ICU) at our institution. A large outbreak of B. cepacia bacteremia involving 95 patients lasted for 4 years in an ICU in northern Taiwan. The clinical characteristics and antimicrobial treatment responses of these patients were analyzed. Minimal inhibitory concentrations
Increasing numbers of new HIV infection is an important issue of public health in Taiwan. We aim ... more Increasing numbers of new HIV infection is an important issue of public health in Taiwan. We aim to evaluate the safety, tolerability and effectiveness of HIV non-occupational prophylaxis (nPEP) in Taiwan. We conducted a prospective cohort observational study between March 2011 and May 2014. Three-combined antiretroviral agents were prescribed for all the persons who sought for HIV post-exposure prophylaxis after high risk sexual behaviour. HIV screening, health education and consultation were done before initiation of nPEP. Adverse effects were evaluated at Weeks 1, 2 and 4 and effectiveness was evaluated at Weeks 12 and 24. We also assessed adherence by pill count and regimen completion rates. During the study periods, 255 persons were enrolled. Among the enrolled cases, 43.9% (112/255) of them received zidovudine (AZT)-based regimen while the others received tenofovir (TDF)-based regimen and the third agent was composed of mostly lopinavir/ritonavir (81.4%). The completion rate o...
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 2014
To retrospectively investigate the incidence of and factors associated with skin rashes and hepat... more To retrospectively investigate the incidence of and factors associated with skin rashes and hepatotoxicity in HIV-infected patients who initiated combination antiretroviral therapy (cART) containing nevirapine plus two nucleos(t)ide reverse-transcriptase inhibitors. The medical records of HIV-infected adult patients who started nevirapine-containing cART and continued follow-up for ≥4 weeks were reviewed at two hospitals in Taiwan between 2000 and 2012. Clinical data obtained at baseline and during follow-up were collected and analyzed. Of the 338 patients included in the analysis, 13.0% tested positive for hepatitis B virus surface antigen and 7.9% tested positive for anti-hepatitis C virus antibody. The incidence of rashes was 21.6% and of hepatotoxicity was 25.5%. On multiple logistic regression analysis, a two-fold or greater increase from the upper limit of normal levels of aminotransferases at baseline was associated with rashes (adjusted odds ratio (aOR) 3.74, 95% confidence ...
Journal of Microbiology, Immunology and Infection, 2014
Nontyphoidal Salmonella (NTS) is an important bacterial etiology of diarrheal disease, and it cau... more Nontyphoidal Salmonella (NTS) is an important bacterial etiology of diarrheal disease, and it causes invasive diseases in immunocompromised hosts. For bacteremia from some species, blood culture with a rapid time to positivity (TTP) is associated with greater mortality. This study investigated TTP of NTS bacteremia and its relationship to clinical parameters and prognosis. Adult patients with NTS bacteremia who were admitted to a tertiary care facility in northern Taiwan from January 2010 to December 2012 were enrolled. Demographics, clinical and microbiological characteristics, and treatment response were reviewed. The TTP for each patient was retrieved from the automated machine. Sixty-six adult patients (mean age, 66.1 years; range, 27-96 years) with NTS bacteremia were identified by the following serogroup distributions: serogroup B (23.4%), serogroup C1 (1.6%), serogroup C2 (6.3%), and serogroup D (68.8%). The in-hospital mortality, 14-day mortality, and 30-day mortality were 15.2%, 7.6%, and 12.1%, respectively. The TTP ranged 6.5-41.7 hours (median: 11.5 hours). Patients with rapid TTP (less than 10 hours), compared to patients without rapid TTP, were more likely to have liver cirrhosis (31.6% vs. 6.4%, p = 0.013), endovascular lesions (21.1% vs. 4.3%, p = 0.05), higher bacteremia score, intensive care unit admission (57.9% vs. 25.5%, p = 0.021), and septic shock (63.2% vs. 12.8%, p < 0.001). There were no significant differences in the in-hospital mortality and 14-day mortality between patients with TTP <10 hours and patients with TTP ≥10 hours. The TTP of blood cultures, interpreted with a cut-off point of <10 hours, in patients with NTS bacteremia may provide useful diagnostic and prognostic information.
The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection d... more The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection drug users (IDUs) in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07_BC had significantly lower viral loads (about 58,000 copies per ml less) than patients with subtype B infection (p = 0.002). The replicative capacity of nine CRF07_BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus) was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag.
The study aimed to investigate the incidence of and associated factors with skin rashes among HIV... more The study aimed to investigate the incidence of and associated factors with skin rashes among HIV-infected Taiwanese patients who received once-daily darunavir (DRV) boosted by ritonavir (RTV) (800/100 mg) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs). We reviewed the medical records of HIV-infected patients who switched to once-daily DRV/RTV-containing regimens between January 2012 and November 2013. Patients who switched from 2 NRTIs plus non-NRTI (nNRTI) or other protease inhibitor (PI) to 2 NRTIs plus PIs other than DRV were chosen as comparators. During the study period, 238 patients who switched to once-daily DRV/RTV-containing regimens (Group A) and 178 patients who switched from 2 NRTIs plus nNRTI or other PI to 2 NRTIs plus PI other than DRV/RTV (Group B) were included. There were no differences between Groups A and B in most of the baseline characteristics. Compared with Group B in which 7 (3.9%) developed rashes after switch to PI other than DRV, 26 patients (10.9%) in Group A developed rashes after a median interval of 14 days of starting DRV/RTV-containing regimens (P = 0.009). In multivariate analysis, patients with a history of rashes related to the previous nNRTI-containing regimens before starting DRV/RTV-containing regimens were more likely to develop rashes with an adjusted odds ratio of 3.53 (95% confidence interval, 1.45-8.62). Once-daily regimens containing DRV/RTV is associated with a higher rate of adverse cutaneous reactions than other PI-containing regimens in HIV-infected Taiwanese, especially in those who have a history of rashes to nNRTI-containing regimens before switch to DRV/RTV-containing regimens.
Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 07_BC has caused s... more Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 07_BC has caused serious HIV-1 epidemics among injecting drug users (IDUs) in East Asia. Little is known about the characteristics of the virus and its impact on disease progression among the infected individuals. In this study, we compared immunological progression between 423 IDUs infected with CRF07_BC and 194 men who have sex with men (MSM) with primary subtype B infection, and a representative full-length CRF07_BC molecular clone, pCRF07_BC, was constructed to characterize the virus. We found that IDUs infected with CRF07_BC had significantly slower immunological progression in the Cox proportional hazards model (hazard ratio: 0.30; 95% confidence interval: 0.13-0.69; P=0.004). The constructed recombinant CRF07_BC viruses had a reduced processing of the Gag/Gag-Pol polyproteins, a decreased incorporation of Vpr in the virus particle, tethering of virus particles on the plasma membrane and decreased virus growth kinetics. These phenotypes are related to the unique 7-amino acid deletion in the p6 of CRF07_BC, since complementation of the 7-amino acid in pCRF07_BC could improve the defective phenotypes. In summary, compared with MSM infected with HIV-1 subtype B, IDUs infected with CRF07_BC had slower immunological progression, which is likely correlated with interference of virus particle maturation by the 7-amino acid deletion in p6.
Journal of Microbiology, Immunology and Infection, 2010
Non-Hodgkin&a... more Non-Hodgkin's lymphoma (NHL) is the second most common acquired immunodeficiency syndrome-defining malignancy with a high mortality rate. This study aimed to describe changes in the incidence and clinical characteristics of NHL in human immunodeficiency virus (HIV)-infected patients in a referral hospital for HIV care. The medical records of HIV-infected patients diagnosed with NHL between June 1994 and December 2006 were retrospectively reviewed. Risk stratification of each patient was evaluated using the International Prognostic Index (IPI). Case patients were followed at least for 2 years to assess the 2-year survival rates. During the 12-year period, 38 HIV-infected patients were diagnosed with NHL. Their median cluster of differentiation 4 count was 82 cells/microL (range, 2-477 cells/microL) at diagnosis. Before the introduction of highly active antiretroviral therapy (HAART) in April 1997, 9/175 HIV-infected patients (5.1%) developed NHL compared with 29/1,386 patients (2.1%) in the HAART era (p < 0.05). Although the 2-year survival rate did not differ significantly between patients diagnosed in the pre-HAART era (22.2%) and those diagnosed in the HAART era (24.1%), patients receiving HAART for more than 6 months had better survival rates (p < 0.05). A low IPI score was a good prognostic factor predictive of a patient's outcome. The incidence of NHL in HIV-infected patients declined significantly in the HAART era. Despite the introduction of HAART, the short-term survival of the patients with NHL remained poor. The IPI was a good predictor for survival.
Journal of Microbiology, Immunology and Infection, 2013
This study aimed to investigate the factors associated with Chlamydia trachomatis infection and t... more This study aimed to investigate the factors associated with Chlamydia trachomatis infection and the genotype distribution of the strains among the clients seeking voluntary counseling and testing (VCT) for human immunodeficiency virus (HIV) in Taiwan. The VCT clients completed an anonymous self-administered questionnaire interview to inquire into the risks for sexually transmitted diseases, followed by providing a 10-mL first-catch urine specimen to detect C. trachomatis with the use of polymerase-chain-reaction assays. The genotyping of C. trachomatis strains was performed by sequencing of omp1 gene. A case-control study was performed to identify factors associated with chlamydial infection. From 2008 to 2011, 140 (4.2%) of the 3323 VCT clients tested positive for C. trachomatis by polymerase chain reaction assays of urine specimens. Compared with 280 control individuals without C. trachomatis infection, cases were more likely to be female (adjusted odds ratio, 3.28; 95% confidence interval, 1.56-6.90) and to report dysuria or urethral discharge (adjusted odds ratio, 2.57; 95% confidence interval, 1.44-4.61). Infections with genotypes Da and G were significantly more common in male than female individuals (genotype Da, 22.2% vs. 0%; and genotype G, 24.4% vs. 3.3%) and in men who have sex with men than heterosexuals (genotype Da, 22.2% vs. 0%; and genotype G, 24.4% vs. 3.3%). Among the VCT clients in Taiwan, female sex and presence of urethral symptoms were associated with C. trachomatis infection of the genitourinary tract. Homosexual male clients were more likely to be infected with genotypes Da and G than heterosexual clients were.
Parkinsonism with myoclonus is rarely associated with infectious disease in adults. We present a ... more Parkinsonism with myoclonus is rarely associated with infectious disease in adults. We present a 55-year-old man experiencing acute onset bilateral limb tremor, rigidity, and myoclonus with small-stepped gait, and skin rash involving the trunk and limbs, after a fever. Serum was positive for anti-Orientia tsutsugamushi immunoglobulin M antibody. Brain MRI revealed no abnormalities. The fever improved with oral doxycycline, and the parkinsonism and myoclonus improved with amantadine and clonazepam. This is a rare case of parkinsonism with myolonus associated with scrub typhus infection.
Dengue virus (DENV) infection triggers the activation of autophagy to facilitate the viral replic... more Dengue virus (DENV) infection triggers the activation of autophagy to facilitate the viral replication cycle from various aspects. Although a number of stimulators are proposed to activate autophagy, none of them appears prior to the uncoating process. Given that T-cell immunoglobulin and mucin domain 1 (TIM-1) receptor is a putative DENV receptor and promotes apoptotic body clearance by autophagy induction, it raises the possibility that TIM-1 may participate in the activation of DENV-induced autophagy. In this study, confocal images first revealed the co-localization of TIM-1 with autophagosomes in DENV-induced autophagy rather than rapamycin-induced autophagy, suggesting the co-transportation of TIM-1 with DENV during infection. The treatment of siRNA to knockdown TIM-1 expression in DENV-infected GFP-microtubule-associated protein light chain 3 (LC3)-Huh7.5 cells revealed that TIM-1 is required not only for DENV cellular internalization but also for autophagy activation. Further...
Journal of Microbiology, Immunology and Infection, 2015
Patients with undetected bacteremia when discharged from a hospital are considered to have occult... more Patients with undetected bacteremia when discharged from a hospital are considered to have occult bacteremia. Klebsiella pneumoniae bacteremia (KPB) is endemic to Taiwan. Our purpose was to study the impact of occult KPB. We retrospectively reviewed the records of patients who were discharged from our emergency department (ED) and subsequently diagnosed with KPB (occult bacteremia), from January 2008 to March 2014. All patients are followed for at least 3 months after the index ED visit. The study group was compared to KPB patients who were directly hospitalized (DH) from ED in 2008. Thirty-day mortality was the primary endpoint. A total of 913 patients were admitted to our ED with KPB, and 88 of these patients (9.6%) had occult KPB. Among them, 43 had second ED visit and 41 were admitted. The overall 30-day mortality was 2.3%. Relative to patients with occult KPB, DH patients had more respiratory tract infections (p < 0.001) but fewer other intra-abdominal infections (p = 0.015). Liver abscess was the major diagnosis for the second ED visit (37.2%). DH patients had significantly greater 30-day mortality than that of overall patients with KPB (19.2% vs.2.3%, p < 0.001). Most patients with occult KPB had favorable outcomes, but about half of them required a second ED visit. Clinicians should aggressively follow patients with occult KPB and should seek to identify the focus of infection in this endemic area.
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi, Jan 31, 2015
Nontyphoid Salmonella (NTS) bacteremia causes high mortality and recurrence rates in human immuno... more Nontyphoid Salmonella (NTS) bacteremia causes high mortality and recurrence rates in human immunodeficiency virus (HIV)-infected patients. This study aimed to investigate the risk of recurrent NTS bacteremia in the era of combination antiretroviral therapy (cART). The medical records of consecutive HIV-infected patients with NTS bacteremia from January 2006 to June 2014 were reviewed. The patients were divided into two groups: patients who achieved a decline of plasma HIV RNA load by ≥ 2 log10 after 4 weeks of cART (good short-term virological response) and those who failed to achieve the goal (poor short-term virological response). Clinical information was collected on the demographics, immunological and virological responses, prophylactic antibiotics used, episodes of recurrent NTS bacteremia, and mortality. During the study period, 49 patients with 52 episodes of NTS bacteremia were included: 29 patients in the good virological response group, in which 16 received secondary proph...
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, Jan 8, 2015
Between 2010 and 2014, we obtained swab specimens to detect Treponema pallidum, with PCR assays, ... more Between 2010 and 2014, we obtained swab specimens to detect Treponema pallidum, with PCR assays, from the oral cavities of 240 patients with 267 episodes of syphilis who reported engaging in unprotected sex practices. The detected treponemal DNA was subjected to genotyping. All of the syphilis cases occurred in men who have sex with men (MSM), and 242 (90.6%) occurred in human immunodeficiency virus-infected patients. The stages of syphilis included 38 cases (14.2%) of primary syphilis of the genital region, 76 (28.5%) of secondary syphilis, 21 (7.9%) of primary and secondary syphilis, 125 (46.8%) of early latent syphilis, and seven (2.6%) others. Concurrent oral ulcers were identified in 22 cases (8.2%). Treponemal DNA was identified from the swabs of 113 patients (42.2%), including 15 (68.2%) with oral ulcers. The most common genotype of T. pallidum was 14f/f. The presence of oral ulcers was associated with identification of T. pallidum in the swab specimens (15/22 (68.2%) vs. 98/...
Diagnostic Microbiology and Infectious Disease, 2011
The purpose of this study was to investigate a cohort of patients with Burkholderia cepacia bacte... more The purpose of this study was to investigate a cohort of patients with Burkholderia cepacia bacteremia in the intensive care unit (ICU) at our institution. A large outbreak of B. cepacia bacteremia involving 95 patients lasted for 4 years in an ICU in northern Taiwan. The clinical characteristics and antimicrobial treatment responses of these patients were analyzed. Minimal inhibitory concentrations
Increasing numbers of new HIV infection is an important issue of public health in Taiwan. We aim ... more Increasing numbers of new HIV infection is an important issue of public health in Taiwan. We aim to evaluate the safety, tolerability and effectiveness of HIV non-occupational prophylaxis (nPEP) in Taiwan. We conducted a prospective cohort observational study between March 2011 and May 2014. Three-combined antiretroviral agents were prescribed for all the persons who sought for HIV post-exposure prophylaxis after high risk sexual behaviour. HIV screening, health education and consultation were done before initiation of nPEP. Adverse effects were evaluated at Weeks 1, 2 and 4 and effectiveness was evaluated at Weeks 12 and 24. We also assessed adherence by pill count and regimen completion rates. During the study periods, 255 persons were enrolled. Among the enrolled cases, 43.9% (112/255) of them received zidovudine (AZT)-based regimen while the others received tenofovir (TDF)-based regimen and the third agent was composed of mostly lopinavir/ritonavir (81.4%). The completion rate o...
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 2014
To retrospectively investigate the incidence of and factors associated with skin rashes and hepat... more To retrospectively investigate the incidence of and factors associated with skin rashes and hepatotoxicity in HIV-infected patients who initiated combination antiretroviral therapy (cART) containing nevirapine plus two nucleos(t)ide reverse-transcriptase inhibitors. The medical records of HIV-infected adult patients who started nevirapine-containing cART and continued follow-up for ≥4 weeks were reviewed at two hospitals in Taiwan between 2000 and 2012. Clinical data obtained at baseline and during follow-up were collected and analyzed. Of the 338 patients included in the analysis, 13.0% tested positive for hepatitis B virus surface antigen and 7.9% tested positive for anti-hepatitis C virus antibody. The incidence of rashes was 21.6% and of hepatotoxicity was 25.5%. On multiple logistic regression analysis, a two-fold or greater increase from the upper limit of normal levels of aminotransferases at baseline was associated with rashes (adjusted odds ratio (aOR) 3.74, 95% confidence ...
Journal of Microbiology, Immunology and Infection, 2014
Nontyphoidal Salmonella (NTS) is an important bacterial etiology of diarrheal disease, and it cau... more Nontyphoidal Salmonella (NTS) is an important bacterial etiology of diarrheal disease, and it causes invasive diseases in immunocompromised hosts. For bacteremia from some species, blood culture with a rapid time to positivity (TTP) is associated with greater mortality. This study investigated TTP of NTS bacteremia and its relationship to clinical parameters and prognosis. Adult patients with NTS bacteremia who were admitted to a tertiary care facility in northern Taiwan from January 2010 to December 2012 were enrolled. Demographics, clinical and microbiological characteristics, and treatment response were reviewed. The TTP for each patient was retrieved from the automated machine. Sixty-six adult patients (mean age, 66.1 years; range, 27-96 years) with NTS bacteremia were identified by the following serogroup distributions: serogroup B (23.4%), serogroup C1 (1.6%), serogroup C2 (6.3%), and serogroup D (68.8%). The in-hospital mortality, 14-day mortality, and 30-day mortality were 15.2%, 7.6%, and 12.1%, respectively. The TTP ranged 6.5-41.7 hours (median: 11.5 hours). Patients with rapid TTP (less than 10 hours), compared to patients without rapid TTP, were more likely to have liver cirrhosis (31.6% vs. 6.4%, p = 0.013), endovascular lesions (21.1% vs. 4.3%, p = 0.05), higher bacteremia score, intensive care unit admission (57.9% vs. 25.5%, p = 0.021), and septic shock (63.2% vs. 12.8%, p < 0.001). There were no significant differences in the in-hospital mortality and 14-day mortality between patients with TTP <10 hours and patients with TTP ≥10 hours. The TTP of blood cultures, interpreted with a cut-off point of <10 hours, in patients with NTS bacteremia may provide useful diagnostic and prognostic information.
The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection d... more The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection drug users (IDUs) in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07_BC had significantly lower viral loads (about 58,000 copies per ml less) than patients with subtype B infection (p = 0.002). The replicative capacity of nine CRF07_BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus) was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag.
The study aimed to investigate the incidence of and associated factors with skin rashes among HIV... more The study aimed to investigate the incidence of and associated factors with skin rashes among HIV-infected Taiwanese patients who received once-daily darunavir (DRV) boosted by ritonavir (RTV) (800/100 mg) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs). We reviewed the medical records of HIV-infected patients who switched to once-daily DRV/RTV-containing regimens between January 2012 and November 2013. Patients who switched from 2 NRTIs plus non-NRTI (nNRTI) or other protease inhibitor (PI) to 2 NRTIs plus PIs other than DRV were chosen as comparators. During the study period, 238 patients who switched to once-daily DRV/RTV-containing regimens (Group A) and 178 patients who switched from 2 NRTIs plus nNRTI or other PI to 2 NRTIs plus PI other than DRV/RTV (Group B) were included. There were no differences between Groups A and B in most of the baseline characteristics. Compared with Group B in which 7 (3.9%) developed rashes after switch to PI other than DRV, 26 patients (10.9%) in Group A developed rashes after a median interval of 14 days of starting DRV/RTV-containing regimens (P = 0.009). In multivariate analysis, patients with a history of rashes related to the previous nNRTI-containing regimens before starting DRV/RTV-containing regimens were more likely to develop rashes with an adjusted odds ratio of 3.53 (95% confidence interval, 1.45-8.62). Once-daily regimens containing DRV/RTV is associated with a higher rate of adverse cutaneous reactions than other PI-containing regimens in HIV-infected Taiwanese, especially in those who have a history of rashes to nNRTI-containing regimens before switch to DRV/RTV-containing regimens.
Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 07_BC has caused s... more Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 07_BC has caused serious HIV-1 epidemics among injecting drug users (IDUs) in East Asia. Little is known about the characteristics of the virus and its impact on disease progression among the infected individuals. In this study, we compared immunological progression between 423 IDUs infected with CRF07_BC and 194 men who have sex with men (MSM) with primary subtype B infection, and a representative full-length CRF07_BC molecular clone, pCRF07_BC, was constructed to characterize the virus. We found that IDUs infected with CRF07_BC had significantly slower immunological progression in the Cox proportional hazards model (hazard ratio: 0.30; 95% confidence interval: 0.13-0.69; P=0.004). The constructed recombinant CRF07_BC viruses had a reduced processing of the Gag/Gag-Pol polyproteins, a decreased incorporation of Vpr in the virus particle, tethering of virus particles on the plasma membrane and decreased virus growth kinetics. These phenotypes are related to the unique 7-amino acid deletion in the p6 of CRF07_BC, since complementation of the 7-amino acid in pCRF07_BC could improve the defective phenotypes. In summary, compared with MSM infected with HIV-1 subtype B, IDUs infected with CRF07_BC had slower immunological progression, which is likely correlated with interference of virus particle maturation by the 7-amino acid deletion in p6.
Journal of Microbiology, Immunology and Infection, 2010
Non-Hodgkin&a... more Non-Hodgkin's lymphoma (NHL) is the second most common acquired immunodeficiency syndrome-defining malignancy with a high mortality rate. This study aimed to describe changes in the incidence and clinical characteristics of NHL in human immunodeficiency virus (HIV)-infected patients in a referral hospital for HIV care. The medical records of HIV-infected patients diagnosed with NHL between June 1994 and December 2006 were retrospectively reviewed. Risk stratification of each patient was evaluated using the International Prognostic Index (IPI). Case patients were followed at least for 2 years to assess the 2-year survival rates. During the 12-year period, 38 HIV-infected patients were diagnosed with NHL. Their median cluster of differentiation 4 count was 82 cells/microL (range, 2-477 cells/microL) at diagnosis. Before the introduction of highly active antiretroviral therapy (HAART) in April 1997, 9/175 HIV-infected patients (5.1%) developed NHL compared with 29/1,386 patients (2.1%) in the HAART era (p < 0.05). Although the 2-year survival rate did not differ significantly between patients diagnosed in the pre-HAART era (22.2%) and those diagnosed in the HAART era (24.1%), patients receiving HAART for more than 6 months had better survival rates (p < 0.05). A low IPI score was a good prognostic factor predictive of a patient's outcome. The incidence of NHL in HIV-infected patients declined significantly in the HAART era. Despite the introduction of HAART, the short-term survival of the patients with NHL remained poor. The IPI was a good predictor for survival.
Journal of Microbiology, Immunology and Infection, 2013
This study aimed to investigate the factors associated with Chlamydia trachomatis infection and t... more This study aimed to investigate the factors associated with Chlamydia trachomatis infection and the genotype distribution of the strains among the clients seeking voluntary counseling and testing (VCT) for human immunodeficiency virus (HIV) in Taiwan. The VCT clients completed an anonymous self-administered questionnaire interview to inquire into the risks for sexually transmitted diseases, followed by providing a 10-mL first-catch urine specimen to detect C. trachomatis with the use of polymerase-chain-reaction assays. The genotyping of C. trachomatis strains was performed by sequencing of omp1 gene. A case-control study was performed to identify factors associated with chlamydial infection. From 2008 to 2011, 140 (4.2%) of the 3323 VCT clients tested positive for C. trachomatis by polymerase chain reaction assays of urine specimens. Compared with 280 control individuals without C. trachomatis infection, cases were more likely to be female (adjusted odds ratio, 3.28; 95% confidence interval, 1.56-6.90) and to report dysuria or urethral discharge (adjusted odds ratio, 2.57; 95% confidence interval, 1.44-4.61). Infections with genotypes Da and G were significantly more common in male than female individuals (genotype Da, 22.2% vs. 0%; and genotype G, 24.4% vs. 3.3%) and in men who have sex with men than heterosexuals (genotype Da, 22.2% vs. 0%; and genotype G, 24.4% vs. 3.3%). Among the VCT clients in Taiwan, female sex and presence of urethral symptoms were associated with C. trachomatis infection of the genitourinary tract. Homosexual male clients were more likely to be infected with genotypes Da and G than heterosexual clients were.
Parkinsonism with myoclonus is rarely associated with infectious disease in adults. We present a ... more Parkinsonism with myoclonus is rarely associated with infectious disease in adults. We present a 55-year-old man experiencing acute onset bilateral limb tremor, rigidity, and myoclonus with small-stepped gait, and skin rash involving the trunk and limbs, after a fever. Serum was positive for anti-Orientia tsutsugamushi immunoglobulin M antibody. Brain MRI revealed no abnormalities. The fever improved with oral doxycycline, and the parkinsonism and myoclonus improved with amantadine and clonazepam. This is a rare case of parkinsonism with myolonus associated with scrub typhus infection.
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Papers by Chia-jui Yang