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Biomedical subjects

K Y Yuen

Publications and source records attributed to K Y Yuen.

At least 19 recordsLinked to original sources
PubMed2006

Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control.

Preparedness for a possible influenza pandemic caused by highly pathogenic avian influenza A subtype H5N1 has become a global priority. The spread of the virus to Europe and continued human infection in Southeast Asia have heightened pandemic concern. It remains unknown from where the pandemic strain may emerge; current attention is directed at Vietnam, Thailand, and, more recently, Indonesia and China. Here, we report that genetically and antigenically distinct sublineages of H5N1 virus have become established in poultry in different geographical regions of Southeast Asia, indicating the long-term endemicity of the virus, and the isolation of H5N1 virus from apparently healthy migratory birds in southern China. Our data show that H5N1 influenza virus, has continued to spread from its established source in southern China to other regions through transport of poultry and bird migration. The identification of regionally distinct sublineages contributes to the understanding of the mechanism for the perpetuation and spread of H5N1, providing information that is directly relevant to control of the source of infection in poultry. It points to the necessity of surveillance that is geographically broader than previously supposed and that includes H5N1 viruses of greater genetic and antigenic diversity.

Animals↗
PubMed2006

Lymphopenia at presentation is associated with increased risk of infections in patients with systemic lupus erythematosus.

BACKGROUND: Patients with systemic lupus erythematosus (SLE) frequently suffer from infections, but the predisposing risk factors, as well as the exact frequency and nature of such infections, are not fully understood. AIM: To describe the frequency, types and risk factors for infections in a group of Chinese patients in the early stage of SLE in Hong Kong. DESIGN: Retrospective record study. METHODS: We reviewed the case records of 91 Chinese SLE patients, presenting <12 months after SLE diagnosis. Details of major infections (requiring intravenous antimicrobial therapy, or any confirmed mycobacterial infection) and minor infections were reviewed. Clinical and laboratory features, the systemic lupus erythematosus disease activity index (SLEDAI) at presentation and drug treatment were recorded and analysed. RESULTS: There were 48 major infections and 62 minor infections during 260 patient-years of follow-up. A lymphocyte count < or =1.0 x 10(9)/l at presentation was independently associated with an increased risk for major infection: hazard ratio 4.7 (95%CI 1.6-13.7), p = 0.005. SLEDAI, use of corticosteroids and immunosuppressive therapy were all not associated with increased risk of infection. DISCUSSION: Lymphopenia was an important risk factor for major infections in this group of Chinese patients in the early stages of SLE. SLE patients with lymphopenia at presentation should be closely monitored for the development of infective complications.

Adolescent↗
PubMed2005

Clinical utility of genotyping resistance test on determining the mutation patterns in HIV-1 CRF01_AE and subtype B patients receiving antiretroviral therapy in Hong Kong.

BACKGROUND: HIV-1 genotypic resistance test (GRT) has been widely used to monitor HIV infection but only few reports revealed the mutation patterns of non-B HIV-1 subtypes. OBJECTIVE: To evaluate the concordance of GRT and clinical treatment outcomes on different HIV-1 subtypes and monitor the mutation patterns and frequencies. STUDY DESIGN: Pre- and post-treatment plasma samples from 123 patients (39 treatment naïve and 84 treatment experienced) were tested by ViroSeq HIV-1 Genotyping System followed by analysis using the Stanford HIV database. The mutation patterns and frequencies developed in the pol gene were compared among subtypes. RESULTS: HIV-1 subtypes among patients in Hong Kong were mainly subtype B and CRF01_AE. Primary mutation was not detected among all pre-treatment samples. For post-treatment samples, primary mutations were only detected in the treatment failure group. The mutation patterns and frequencies were similar between CRF01_AE and subtype B viruses. However, the frequencies of L74V/I and K103N in the reverse transcriptase region were different between CRF01_AE and subtype B viruses. VirtualPhenotype was unable to analyze an in-frame insertion of arginine and isoleucine at protease codon 35 of one CRF01_AE isolate. CONCLUSIONS: This is the first report to demonstrate the high degree of concordance of longitudinal genotyping data and clinical treatment outcome in patients harboring different HIV-1 subtypes. Our findings shed light to the emergence of resistance mutations and its testing in CRF01_AE, which is relevant to other prevailing places in Asia.

Algorithms↗
PubMed2005

Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study.

BACKGROUND: Clarithromycin is frequently used to treat community-acquired pneumonia in elderly persons. Like erythromycin, it may interact with other drugs by interfering with metabolism by cytochrome P450 enzymes and with the P-glycoprotein transporter system. Colchicine, used for treatment of acute gout and for prophylaxis, may cause bone marrow toxicity. It is metabolized by CYP3A4 and is transported by P-glycoprotein. Initial case reports suggested potentially fatal interactions between clarithromycin and colchicine. METHODS: A retrospective study was conducted with 116 patients who were prescribed clarithromycin and colchicine during the same clinical admission. Case-control comparisons were made between patients who received concomitant therapy with the 2 drugs and patients who received sequential therapy. We assessed the clinical presentations and outcomes of the 2 patient groups and analyzed the risk factors associated with fatal outcomes. RESULTS: Nine (10.2%) of the 88 patients who received the 2 drugs concomitantly died. Only 1 (3.6%) of the 28 patients who received the drugs sequentially died. Multivariate analysis of the 88 patients who received concomitant therapy showed that longer overlapped therapy (relative risk [RR], 2.16; 95% confidence interval [CI], 1.41-3.31; P< or =.01), the presence of baseline renal impairment (RR, 9.1; 95% CI, 1.75-47.06; P<.001), and the development of pancytopenia (RR, 23.4; 95% CI, 4.48-122.7; P<.001) were independently associated with death. CONCLUSIONS: Clarithromycin increases the risk of fatal colchicine toxicity, especially for patients with renal insufficiency. Since there are other drugs for treatment of pneumonia and gout, these 2 drugs should not be coprescribed, because of the risk of fatality.

Aged↗
PubMed2005

Occurrence and molecular analysis of extended-spectrum {beta}-lactamase-producing Proteus mirabilis in Hong Kong, 1999-2002.

OBJECTIVES: A study was conducted to evaluate the occurrence and characterization of extended-spectrum beta-lactamases (ESBLs) among blood isolates of Proteus mirabilis collected over a 4 year period in Hong Kong. METHODS: Production of ESBLs among 99 consecutive and non-duplicate isolates was evaluated by the double-disc synergy test. The ESBLs were characterized by isoelectric focusing and PCR sequencing using specific primers. The epidemiological relationship of the isolates was studied by the Dienes test and PFGE. RESULTS: ESBLs were identified in 13 isolates, from none in 1999-2000 and up to 18.5% (5/27) in 2001 and 25.8% (8/31) in 2002. The ESBL-producing isolates were more resistant to ceftriaxone than to ceftazidime, and were more likely than non-ESBL-producers to have resistance to ciprofloxacin (76.9% versus 14%) and gentamicin (38.5% versus 9.3%). The ESBL content included CTX-M-13 (n=8), CTX-M-14 (n=3), SHV-5 (n=2), TEM-11 (n=1), and an unidentified ESBL with a pI of 7.5. The Dienes test revealed that the genetic background in the 99 isolates was highly heterogeneous, with 54 distinct types among 92 isolates and seven were non-typeable. Among the 13 ESBL-producing isolates, five different backgrounds, including one cluster (Dienes-pulsotype A) with nine isolates, were identified by both Dienes test and PFGE, thus suggesting both clonal and multi-clonal spread of the CTX-M enzymes. CONCLUSIONS: Our findings indicate the emergence of CTX-M enzymes among P. mirabilis in Hong Kong. More ESBL screening of this species is required to improve their recognition.

Drug Resistance, Bacterial↗
PubMed2005

Molecular diagnostics in tuberculosis.

Molecular diagnostics in tuberculosis has enabled rapid detection of Mycobacterium tuberculosis complex in clinical specimens, identification of mycobacterial species, detection of drug resistance, and typing for epidemiological investigation. In the laboratory diagnosis of tuberculosis, the nucleic acid amplification (NAA) test is rapid and specific but not as sensitive as culture of mycobacteria. The primary determinant of successful NAA testing for tuberculosis depends on the shedding of mycobacterial DNA in secretions from caseating granulomas and its dissemination into sterile body fluids or tissue biopsies. In multibacillary diseases with a high mycobacterial load, a positive Ziehl-Neelsen smear with a positive NAA test is diagnostic of active tuberculosis, whereas a positive Ziehl-Neelsen smear with a negative NAA test in the absence of inhibitors would indicate nontuberculous mycobacterial disease. The role of the NAA test is more important in paucibacillary diseases with low mycobacterial loads. The presence of polymerase chain reaction (PCR) inhibitors, however, especially in extrapulmonary specimens, may produce false-negative results. Although this problem can be overcome to some extent by extra extraction steps, the additional processing invariably leads to the loss of mycobacterial DNA. To circumvent this problem, a brief culture augmentation step is carried out before the NAA test is performed, which can enhance the mycobacterial load while concomitantly diluting inhibitors, thereby maintaining the sensitivity of the test without excessively increasing turnaround time.

Microbial Sensitivity Tests↗
PubMed2005

Clinical evaluation of real-time PCR assays for rapid diagnosis of SARS coronavirus during outbreak and post-epidemic periods.

BACKGROUND: The protocols of WHO network laboratories facilitated development of rapid diagnosis for SARS coronavirus (CoV) using reverse transcription (RT)-PCR assays. However, several reports have shown that conventional and real-time PCR assays were very specific for SARS CoV but lack sensitivity depending on the assay, specimen, and time course of disease. OBJECTIVE: To evaluate an automatic nucleic acid extraction system and two standardized real-time PCR assays for rapid diagnosis of SARS CoV during outbreak and post-epidemic periods in Hong Kong. STUDY DESIGN: Specimens from clinically suspected SARS patients collected during outbreak and post-epidemic periods were tested by an automatic nucleic acid extraction system followed by our first generation conventional RT-PCR and two standardized real-time PCR assays (Artus GmbH, Germany and Roche Diagnostics, Germany). Paired serum samples were assayed for increasing titer against SARS CoV. RESULTS: In the SARS epidemic, Artus and Roche PCR assays exhibited sensitivities of 87% and 85% for respiratory specimens (n = 64), 91% and 88% for stool (n = 44), and 82% for urine (n = 29). A specificity of 100% was exhibited by both PCR assays except Artus attained only a 92% specificity for stool. For post-epidemic period, no SARS CoV was identified among 56 respiratory specimens by all PCR assays. Inhibitors to PCR assays were detected at an average rate of 7-8% among 202 clinical specimens. CONCLUSION: This study highlights the high throughput and performance of automatic RNA extraction in coordination with standardized real-time PCR assays suitable for large-scale routine diagnosis in case of future SARS epidemic. As no SARS CoV was detected among specimens collected during post-epidemic period, the positive predictive value of real-time PCR assays for detection of SARS CoV during low epidemic requires further evaluation.

Disease Outbreaks↗
PubMed2005

The severe acute respiratory syndrome (SARS).

The world was shocked in early 2003 when a pandemic of severe acute respiratory syndrome (SARS) was imminent. The outbreak of this novel disease, caused by a novel coronavirus (the SARS-coronavirus), hit hardest in the Asian Pacific region, though eventually it spread to five continents. The speed of the spread of the SARS epidemic was unprecedented due to the highly efficient intercontinental transportation. An international collaborative effort through the World Health Organization (WHO) has helped to identify the aetiological agent about 1 month after the onset of the epidemic. The power of molecular biology and bioinformatics has enabled the complete decoding of the viral genome within weeks. Over 1000 publications on the phylogeny, epidemiology, genomics, laboratory diagnostics, antiviral, immunization, pathogenesis, clinical disease, and management accumulated within just 1 year. Although the exact animal reservoir of virus and how it evolved into a human pathogen are still obscure, accurate diagnosis and epidemiological control of the disease are now possible. This article reviews what is currently known about the virus and the disease.

Animals↗
PubMed2005

Serological responses in patients with severe acute respiratory syndrome coronavirus infection and cross-reactivity with human coronaviruses 229E, OC43, and NL63.

The serological response profile of severe acute respiratory syndrome (SARS) coronavirus (CoV) infection was defined by neutralization tests and subclass-specific immunofluorescent (IF) tests using serial sera from 20 patients. SARS CoV total immunoglobulin (Ig) (IgG, IgA, and IgM [IgGAM]) was the first antibody to be detectable. There was no difference in time to seroconversion between the patients who survived (n = 14) and those who died (n = 6). Although SARS CoV IgM was still detectable by IF tests with 8 of 11 patients at 7 months postinfection, the geometric mean titers dropped from 282 at 1 month postinfection to 19 at 7 months (P = 0.001). In contrast, neutralizing antibody and SARS CoV IgGAM and IgG antibody titers remained stable over this period. The SARS CoV antibody response was sometimes associated with an increase in preexisting IF IgG antibody titers for human coronaviruses OC43, 229E, and NL63. There was no change in IF IgG titer for virus capsid antigen from the herpesvirus that was used as an unrelated control, Epstein-Barr virus. In contrast, patients who had OC43 infections, and probably also 229E infections, without prior exposure to SARS CoV had increases of antibodies specific for the infecting virus but not for SARS CoV. There is a need for awareness of cross-reactive antibody responses between coronaviruses when interpreting IF serology.

Adult↗
PubMed2005

Human infection with an avian H9N2 influenza A virus in Hong Kong in 2003.

Avian H9N2 influenza A virus has caused repeated human infections in Asia since 1998. Here we report that an H9N2 influenza virus infected a 5-year-old child in Hong Kong in 2003. To identify the possible source of the infection, the human isolate and other H9N2 influenza viruses isolated from Hong Kong poultry markets from January to October 2003 were genetically and antigenically characterized. The findings of this study show that the human H9N2 influenza virus, A/Hong Kong/2108/03, is of purely avian origin and is closely related to some viruses circulating in poultry in the markets of Hong Kong. The continued presence of H9N2 influenza viruses in poultry markets in southern China increases the likelihood of avian-to-human interspecies transmission.

Antigens, Viral↗
PubMed2005

Identification of a novel coronavirus in bats.

Exotic wildlife can act as reservoirs of diseases that are endemic in the area or can be the source of new emerging diseases through interspecies transmission. The recent emergence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) highlights the importance of virus surveillance in wild animals. Here, we report the identification of a novel bat coronavirus through surveillance of coronaviruses in wildlife. Analyses of the RNA sequence from the ORF1b and S-gene regions indicated that the virus is a group 1 coronavirus. The virus was detected in fecal and respiratory samples from three bat species (Miniopterus spp.). In particular, 63% (12 of 19) of fecal samples from Miniopterus pusillus were positive for the virus. These findings suggest that this virus might be commonly circulating in M. pusillus in Hong Kong.

Amino Acid Sequence↗
PubMed2005

Pulmonary artery thrombosis in a patient with severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is an emerging infectious disease with both pulmonary and extra-pulmonary manifestations. Although coagulation abnormalities are common in these patients, clinically overt thromboembolic events are rarely reported. This report describes the first case of pulmonary artery thrombosis in a patient with laboratory confirmed SARS.

Adult↗
PubMed2005

Duration of RT-PCR positivity in severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a highly infectious respiratory infection with a high mortality. The duration of infectivity is unknown. The RT-PCR positivity for SARS-associated coronavirus (SARS-CoV) was followed in 45 virologically confirmed SARS patients. Serial RT-PCRs for SARS-CoV were performed in the nasopharyngeal aspirate, stool and urine of 45 SARS patients who survived until discharge. All patients had at least one site that was positive for SARS-CoV on presentation. Time to RT-PCR conversion was studied in all patients. There were 15 males (33.3%) and 30 females (66.7%), with a mean+/- SD age of 40.7+/-14.7 yrs. The median (range) time of RT-PCR conversion was 30 days (2-81). On discharge from the hospital, 18 (40%) remained RT-PCR positive in at least one site. For patients with positive RT-PCR on discharge, the median (range) time to RT-PCR conversion after discharge was 13 days (2-60). A significant proportion of severe acute respiratory syndrome patients remained RT-PCR positive for severe acute respiratory syndrome-associated coronavirus for a substantial duration after discharge. The clinical significance is unknown and this finding merits further study. It is prudent to advise patients to adhere to strict personal hygiene on discharge until RT-PCR becomes negative.

Adolescent↗