Liu Ch

Chromosome and bcr rearrangement in chronic myelogenous leukaemia and their correlation with clinical states and prognosis of the disease

Summary. Among 77 unselected patients with chronic myelogenous leukaemia (CML), 70 had Philadelphia chromosome (Ph1) in blood cells. Extra chromosomal abnormalities were noted in 4%, 55% and 78% of Ph1‐positive patients in chronic phase, accelerated phase and acute blast crisis, respectively. Rearrangement of the bcr was detected in 46 of 47 Ph1‐positive patients studied and also in three of five Ph1‐negative ones. The locations of the breakpoints were mapped to one of four zones of the bcr in 45 patients. The median duration from diagnosis of CML to onset of acute blast crisis was not significantly different between the two groups of patients with breakpoints in the 5’portion (34 months), and in the 3’portion (39 months) of the bcr. In addition, the locations of the breakpoints within the bcr did not change as the disease progressed in the six patients who had DNA analysed both in the chronic phase and subsequently in transformation. In one of them, an additional aberrant band which was not present in the beginning of the acute phase was detected in blood cells taken 2 months later. It is suggested from the studies that transformation of CML may not be related to alterations within the bcr.

Seroprevalence of chronic hepatitis B virus infection among taiwanese human immunodeficiency virus type 1-positive persons in the era of nationwide hepatitis B vaccination.

OBJECTIVES:We aimed to assess the impact of nationwide hepatitis B virus (HBV) vaccination program on the seroprevalence of HBV infection among human immunodeficiency virus (HIV)–positive persons in a country where most HBV exposure occurs during the perinatal period or in early childhood.METHODS:Data on HBV surface antigen (HBsAg), anti-HBV surface (anti-HBs), anti-HBV core (anti-HBc), and anti-hepatitis C virus (anti-HCV) antibody were retrospectively collected from 3,164 HIV-positive and 2,594 HIV-negative persons between 2004 and 2007. Comparisons of serological markers of HBV and HCV were made between HIV-positive and -negative adults born before and after the implementation of the HBV vaccination program in Taiwan in July 1984.RESULTS:Compared with HIV-negative persons, the adjusted odds ratio for HBsAg seropositivity was 1.100 (95% confidence interval, 0.921–1.315) among HIV-positive persons. Although the seroprevalence of anti-HCV antibody remained similar between HIV-positive persons born before and those born after 1984, the seroprevalence of HBsAg declined from 20.3 to 3.3% in HIV-positive persons (P<0.001) and from 15.5 to 8.5% in HIV-negative persons (P<0.001). Despite the high seroprevalence of anti-HCV antibody (97.1%) in HIV-positive injecting drug users (IDUs), there was no statistically significant difference in the seroprevalence of HBsAg (5.6% vs. 8.5%, P=0.75) or anti-HBc antibody (40.7% vs. 27.9%, P=0.14) between HIV-positive IDUs and HIV-negative persons who were born after 1984.CONCLUSIONS:Our study showed a significant decline of seroprevalence of HBV infection among both HIV-negative and -positive persons who were born in the era of the nationwide HBV vaccination in Taiwan.

Multicenter Study of Trimethoprim/Sulfamethoxazole-Related Hepatotoxicity: Incidence and Associated Factors among HIV-Infected Patients Treated for Pneumocystis jirovecii Pneumonia

The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145–0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV-infected Taiwanese patients who received TMP/SMX for pneumocystosis. Concomitant use of fluconazole was associated with decreased risk for TMP/SMX-related hepatotoxicity.

Subcutaneous infection caused by Corynespora cassiicola, a plant pathogen

We describe a 69-year-old female farmer with diabetes mellitus who developed subcutaneous infection due to a plant pathogen, Corynespora cassiicola. The organism was identified based on characteristic morphotypes and confirmed by sequence analysis of the internal transcribed spacer (ITS) regions. The patient was treated successfully with amphotericin B therapy.

Hepatitis A virus infection and hepatitis A vaccination in human immunodeficiency virus-positive patients: A review

Hepatitis A virus (HAV) is one of the most common infectious etiologies of acute hepatitis worldwide. The virus is known to be transmitted fecal-orally, resulting in symptoms ranging from asymptomatic infection to fulminant hepatitis. HAV can also be transmitted through oral-anal sex. Residents from regions of low endemicity for HAV infection often remain susceptible in their adulthood. Therefore, clustered HAV infections or outbreaks of acute hepatitis A among men who have sex with men and injecting drug users have been reported in countries of low endemicity for HAV infection. The duration of HAV viremia and stool shedding of HAV may be longer in human immunodeficiency virus (HIV)-positive individuals compared to HIV-negative individuals with acute hepatitis A. Current guidelines recommend HAV vaccination for individuals with increased risks of exposure to HAV (such as from injecting drug use, oral-anal sex, travel to or residence in endemic areas, frequent clotting factor or blood transfusions) or with increased risks of fulminant disease (such as those with chronic hepatitis). The seroconversion rates following the recommended standard adult dosing schedule (2 doses of HAVRIX 1440 U or VAQTA 50 U administered 6-12 mo apart) are lower among HIV-positive individuals compared to HIV-negative individuals. While the response rates may be augmented by adding a booster dose at week 4 sandwiched between the first dose and the 6-mo dose, the need of booster vaccination remain less clear among HIV-positive individuals who have lost anti-HAV antibodies.

Multicenter study of skin rashes and hepatotoxicity in antiretroviral-naïve HIV-positive patients receiving non-nucleoside reverse-transcriptase inhibitor plus nucleoside reverse-transcriptase inhibitors in Taiwan

Objectives Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs. Methods Between June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study. According to the national HIV treatment guidelines, patients were assessed at baseline, 2 and 4 weeks of cART initiation, and subsequently every 8 to 12 weeks. Plasma HIV RNA load, CD4 cell count and aminotransferases were determined. The toxicity grading scale of the Division of AIDS (DAIDS) 2014 was used for reporting clinical and laboratory adverse events. Results During the 3.5-year study period, 2,341 patients initiated nNRTI-containing cART: NVP in 629 patients, EFV 1,363 patients, and RPV 349 patients. Rash of any grade occurred in 14.1% (n = 331) of the patients. In multiple logistic regression analysis, baseline CD4 cell counts (per 100-cell/μl increase, adjusted odds ratio [AOR], 1.125; 95% confidence interval [95% CI], 1.031–1.228) and use of NVP (AOR, 2.443; 95% CI, 1.816–3.286) (compared with efavirenz) were independently associated with the development of skin rashes. Among the 1,455 patients (62.2%) with aminotransferase data both at baseline and week 4, 72 (4.9%) developed grade 2 or greater hepatotoxicity. In multiple logistic regression analysis, presence of antibody for hepatitis C virus (HCV) (AOR, 2.865; 95% CI, 1.439–5.704) or hepatitis B surface antigen (AOR, 2.397; 95% CI, 1.150–4.997), and development of skin rashes (AOR, 2.811; 95% CI, 1.051–7.521) were independently associated with the development of hepatotoxicity. Conclusions The baseline CD4 cell counts and use of NVP were associated with increased risk of skin rashes, while hepatotoxicity was independently associated with HCV or hepatitis B virus coinfection, and development of skin rashes in antiretroviral-naïve HIV-positive Taiwanese patients within 4 weeks of initiation of nNRTI-containing regimens.

Trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus causing invasive infections in Taiwan: results from the Tigecycline in vitro Surveillance in Taiwan (TIST) study, 2006-2010.

This study was intended to investigate the trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) causing invasive infections. A total of 670 MRSA isolates were collected from patients with invasive infections as part of bacterial collection in the Tigecycline in vitro Surveillance in Taiwan (TIST) from 2006 to 2010. MICs of the isolates to vancomycin were determined using the agar dilution method. Characteristics of staphylococcal cassette chromosome mec (SCCmec), mec-associated hypervariable region (dru), and accessory gene regulator (agr) of the isolates were identified by polymerase chain reaction methods. MRSA isolates with SCCmec types I, II, and III were molecularly defined as hospital-associated MRSA (HA-MRSA), and those with SCCmec types IV, V, and VT were assigned as community-associated MRSA (CA-MRSA). All but 1 MRSA isolates exhibited vancomycin MICs ≤1 mg/L. A declining trend in vancomycin MICs among MRSA isolates was noted, which was associated with the decline in proportion of HA-MRSA. The percentage of CA-MRSA increased from 25.6% in 2006 to 46.0% in 2010. An increase in the geometric mean of vancomycin MICs was found in MRSA with particular molecular types such as SCCmec types II and III, agr groups I and II, and dru10-14. A significant correlation among particular molecular types was found, including SCCmecII-agr group II-dru4, SCCmecIII-agr group I-dru11-14, SCCmecIV-agr group II-dru9, and SCCmecVT-agr group I-dru9 and dru11. There was no vancomycin creep among MRSA isolates, and the declining trend of vancomycin MIC against MRSA was attributed to the increasing prevalence of CA-MRSA over time.

Evolution of hepatitis A virus seroprevalence among HIV-positive adults in Taiwan.

Objectives The study aimed to describe the seroprevalence of hepatitis A virus (HAV) in HIV-positive adult patients in Taiwan between 2012 and 2016 and to examine the evolution of HAV seroprevalence between 2004–2007 and 2012–2016. Methods Clinical information and data of anti-HAV antibody results were collected from 2,860 antiretroviral-naïve HIV-positive Taiwanese aged 18 years or older who initiated combination antiretroviral therapy at 11 hospitals around Taiwan between 2012 and 2016 (2012–2016 cohort). A multivariate logistic regression model was applied to identify independent variables associated with HAV seropositivity. Comparisons of HAV seroprevalences and associated clinical characteristics were made between this 2012–2016 cohort and a previous cohort of 1580 HIV-positive patients in 2004–2007 (2004–2007 cohort). Results Of the 2,860 HIV-positive patients between 2012 and 2016, the overall HAV seropositivity rate was 21.2% (605/2860), which was independently associated with an older age (adjusted odds ratio [AOR], per 1-year increase, 1.13; 95% confidence interval [95% CI], 1.11–1.15) and co-infection with hepatitis B virus (AOR 1.44; 95% CI, 1.08–1.93). Residence in southern Taiwan (AOR 0.49; 95% CI, 0.34–0.72) was inversely associated with HAV seropositivity. The overall HAV seroprevalence in the 2012–2016 cohort was significantly lower than that in the 2004–2007 cohort (21.2% vs 60.9%, p<0.01). The decreases of HAV seropositivity rate were observed in nearly every age-matched group, which suggested the cohort effect on HAV seroepidemiology. However, among individuals aged 25 years or younger, the HAV seropositivity rate increased from 3.8% (2/52) in the 2004–2007 cohort to 8.5% (50/587) in the 2012–2016 cohort, with 95.4% (560/587) being MSM in this age group of the latter cohort. Conclusions HAV seroprevalence has decreased with time among HIV-positive adults in Taiwan. The cohort effect has increased the number of young HIV-positive patients that are susceptible to HAV infection in a country without nationwide childhood vaccination program against HAV.

Epidemiology and antifungal susceptibility of candidemia isolates of non-albicans Candida species from cancer patients

Candidemia is a growing concern worldwide, and its species distribution has shifted toward non-albicans Candida in recent decades, especially in patients with malignancy. This study aimed to update the epidemiology and antifungal susceptibility of non-albicans candidemia isolates from the cancer patients. Adult cancer patients with non-albicans candidemia were recruited, and clinical data were retrospectively collected from five medical centers in Taiwan from 1 July 2011 to 30 June 2014. In vitro susceptibility was determined by the broth dilution method using a Sensititre YeastOne system and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. A total of 346 episodes of non-albicans candidemia were identified in cancer patients. Candida tropicalis was the most common species (n=145, 41.9%) and had the highest resistance rate to fluconazole (n=17, 13.9%) among all the preserved isolates, including C. tropicalis, Candida glabrata and Candida parapsilosis. A higher Charlson comorbidity index, non-albicans candidemia due to C. tropicalis, neutropenia and septic shock were independent predictors of 28-day mortality. In conclusion, the species distribution and antifungal susceptibility of non-albicans candidemia isolates in our study differed from those in Western countries, providing useful information about local epidemiology for the selection of empirical antifungal agents for cancer patients.

Are we ready for the global emergence of multidrug-resistant Candida auris in Taiwan?

Candida auris is a recently identified multi-resistant Candida species, first reported in Japan in 2009, and poses a serious global health threat. Lack of awareness of this new Candida species and difficulties with laboratory identification have impacted significantly on outbreak detection and management, and compromised patient outcome. Accordingly, there is an urgent need to raise awareness of healthcare personnel to this emerging pathogen and determine its prevalence, impact, and challenges to the Taiwan healthcare system. Enhanced laboratory testing strategies are needed to differentiate C. auris from other Candida species to provide accurate diagnosis and implement control measures early enough to prevent hospital outbreaks. In this report, we review the key epidemiological, microbiological and clinical characteristics of C. auris and provide the results of a multicenter surveillance study of C. auris in Taiwan. We also conducted a web-based survey to determine awareness of the medical community to C. auris and the capability of Taiwanese hospital laboratories to identify this microorganism. C. auris has not yet been isolated from humans in Taiwan, but the unique features of this microorganism and its ability to reach across international boundaries justify the importance of these initiatives in Taiwan.