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As the COVID-19 pandemic progresses, there is an increasing need for rapid, accessible assays for SARS-CoV-2 detection. We present a clinical evaluation and real-world implementation of the INDICAID COVID-19 rapid antigen test (INDICAID rapid test). A multisite clinical evaluation of the INDICAID rapid test using prospectively collected nasal (bilateral anterior) swab samples from symptomatic subjects was performed. The INDICAID rapid test demonstrated a positive percent agreement (PPA) and negative percent agreement (NPA) of 85.3% (95% confidence interval [95% CI], 75.6% to 91.6%) and 94.9% (95% CI, 91.6% to 96.9%), respectively, compared to laboratory-based reverse transcriptase PCR (RT-PCR) using nasal specimens. The INDICAID rapid test was then implemented at COVID-19 outbreak screening centers in Hong Kong as part of a testing algorithm (termed "dual-track") to screen asymptomatic individuals for prioritization for confirmatory RT-PCR testing. In one approach, preliminary positive INDICAID rapid test results triggered expedited processing for laboratory-based RT-PCR, reducing the average time to confirmatory result from 10.85 h to 7.0 h. In a second approach, preliminary positive results triggered subsequent testing with an onsite rapid RT-PCR, reducing the average time to confirmatory result to 0.84 h. In 22,994 asymptomatic patients, the INDICAID rapid test demonstrated a PPA of 84.2% (95% CI, 69.6% to 92.6%) and an NPA of 99.9% (95% CI, 99.9% to 100%) compared to laboratory-based RT-PCR using combined nasal/oropharyngeal specimens. The INDICAID rapid test has excellent performance compared to laboratory-based RT-PCR testing and, when used in tandem with RT-PCR, reduces the time to confirmatory positive result. IMPORTANCE Laboratory-based RT-PCR, the current gold standard for COVID-19 testing, can require a turnaround time of 24 to 48 h from sample collection to result. The delayed time to result limits the effectiveness of centralized RT-PCR testing to reduce transmission and stem potential outbreaks. To address this, we conducted a thorough evaluation of the INDICAID COVID-19 rapid antigen test, a 20-minute rapid antigen test, in both symptomatic and asymptomatic populations. The INDICAID rapid test demonstrated high sensitivity and specificity with RT-PCR as the comparator method. A dual-track testing algorithm was also evaluated utilizing the INDICAID rapid test to screen for preliminary positive patients, whose samples were then prioritized for RT-PCR testing. The dual-track method demonstrated significant improvements in expediting the reporting of positive RT-PCR test results compared to standard RT-PCR testing without prioritization, offering an improved strategy for community testing and controlling SARS-CoV-2 outbreaks.

Community-associated methicillin resistant Staphylococcus aureus is an emerging cause of skin and soft tissue infections in Hong Kong, especially among certain ethnic minorities.

1. Community-associated methicillin-resistant Staphylococcus aureus (MRSA) strains with diverse genetic backgrounds are emerging in Hong Kong. 2. Intra-familial spread of community-associated MRSA is common.

Objectives: To study the prevalence of commonly occurring infections among residents of residential care homes for the elderly and their associated risk factors., Design: Point prevalence survey., Setting: Residential care homes for the elderly in Hong Kong., Participants: Residential care homes for the elderly were treated as a cluster and about 30% of the residents from each home were selected by systematic sampling with bed numbers ending with the digits of 2, 5, and 8. Selected residents were invited to participate., Results: Data from 1603 residents aged 60 years or older from 43 residential care homes for the elderly were analysed. Most (85%) of the residents had underlying medical problems and 55% had more than one problem. The overall prevalence of infection among these residents was 5.7% (95% confidence interval, 4.2-7.1%). The three most common infections were: common cold or pharyngitis (1.9%; 95% confidence interval, 0.9-3.0%), skin and soft-tissue infections (1.4%; 0.5-2.4%), and symptomatic urinary tract infections (0.6%; 0.2-0.9%). Being 'bed-ridden' was a significant risk factor for skin and soft-tissue infections (odds ratio=3.1; 95% confidence interval, 1.4-6.9). Presence of a urinary catheter was a significant risk factor for symptomatic urinary tract infections (odds ratio=62.8; 95% confidence interval, 18.2-217.0). Chronic obstructive pulmonary disease was a significant risk factor for lower respiratory tract infection (odds ratio=16.5; 95% confidence interval, 3.4-81.2)., Conclusions: This is the first territory-wide prevalence survey of infections among residents in residential care homes for the elderly in Hong Kong. The data retrieved enable us to target our infection control programme in residential care homes for the elderly to those with a high prevalence. So as to monitor seasonal and secular trends, targeted regular surveillance is needed for better profiling of the actual situation.

This prospective study assessed the epidemiology of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) among patients with purulent skin and soft tissue infections (SSTIs) in Hong Kong. Among 298 patients with SSTIs, 10.4% (13/125) of all S. aureus isolates and 5% (12/241) of all abscesses were attributed to pvl-positive CA-MRSA. Overall, 77% and 69.9% of CA-MRSA and methicillin-sensitive S. aureus (MSSA) were susceptible to erythromycin, 77% and 74.8% to clindamycin, 100% and 97.1% to minocycline, and 100% and 98.1% to rifampin, respectively. Filipino ethnicity was the only clinical and epidemiologic factor significantly associated with CA-MRSA infection (odds ratio, 14.8; 95% confidence interval, 3.3-70.0; P < 0.001). Pulsed-field gel electrophoresis analysis showed that 6 CA-MRSA isolates belonged to the ST30-HKU100 clone, 5 belonged to the ST59-HKU200 clone, and 1 was singleton. Features of HKU100 isolates include SCCmec type IV, agr3, spa t019, and pan-susceptibility to non-beta-lactam antibiotics. In contrast, HKU200 isolates are characterized by having SCCmec type IV or V, agr4, spa t437, and variable non-beta-lactam susceptibility profiles. The major CA-MRSA spa types were shared by a minority of the MSSA.

This territory-wide study evaluated the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in residential care homes for elderly (RCHEs) in Hong Kong. MRSA colonization was assessed by taking swab culture from anterior nares and active skin lesions. Of 487 RCHEs surveyed, 80 MRSA strains were recovered from 1563 residents, giving a prevalence of 5.1%. Twenty-four isolates had SCCmec II, 2 had SCCmec III, 17 had SCCmec IV, 36 had SCCmec V, and 1 had a composite SCCmec type. Pulsed-field gel electrophoresis typing clustered 75 isolates into 7 clones (HKU10 to 50, HKU80, and HKU90). Two predominant types, HKU30 and HKU50, which together account for 75% of all MRSA strains, were found in 13 and 15 of the 18 geographic districts in Hong Kong, respectively. The main features for HKU50 strains were spa t1081/ST45-IV or V, capsular type 8, agrIV, and hla, seg, sei positive. On the other hand, HKU30 strains had spa t002/ST5-II, capsular type 5, agrII, and were hla, seg, sei positive. HKU30 strains were often multidrug resistant (MDR, involving ciprofloxacin, erythromycin, gentamicin, and tetracycline). In contrast, HKU50 strains exhibit both multidrug resistance (MDR) (involving ciprofloxacin, erythromycin, and tetracycline, but not gentamicin) and non-MDR patterns.

Norovirus outbreaks occur worldwide every year and have become more frequent over the last few years. There were extensive outbreaks in Hong Kong from May to July 2006 and our aim was to describe nosocomial outbreaks from 1 May 2006 to 31 July 2006 in this retrospective observational study. A total of 38 confirmed norovirus outbreaks involving 218 patients were identified. Most of these patients were elderly with a mean age of 74.5 years (range: 3 months to 97 years); 62% of them were either totally or partially dependent for help with daily activities, 83.9% had underlying chronic medical problems and 56% had limited mobility. In all, 97.2% of individuals presented with diarrhoea and only 46.3% of them had vomiting. The median duration for diarrhoea was 3 days and the longest 24 days. The median duration of vomiting was one day and the longest 15 days. Fever occurred in one-third of all cases. Reverse transcriptase-polymerase chain reaction was positive for norovirus in 72.6% cases. We conclude that nosocomial norovirus infection often involves frail elderly patients with limited mobility and that these patients may have more prolonged symptoms.

Background: Chemokines play important roles in inflammation and antiviral action. We examined whether polymorphisms of RANTES, IP-10 and Mig affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS)., Methods: We tested the polymorphisms of RANTES, IP-10 and Mig for their associations with SARS in 495 Hong Kong Chinese SARS patients and 578 controls. Then we tried to confirm the results in 356 Beijing Chinese SARS patients and 367 controls., Results: RANTES -28 G allele was associated with SARS susceptibility in Hong Kong Chinese (P < 0.0001, OR = 2.80, 95%CI:2.11-3.71). Individuals with RANTES -28 CG and GG genotypes had a 3.28-fold (95%CI:2.32-4.64) and 3.06-fold (95%CI:1.47-6.39) increased risk of developing SARS respectively (P < 0.0001). This -28 G allele conferred risk of death in a gene-dosage dependent manner (P = 0.014) with CG and GG individuals having a 2.12-fold (95% CI: 1.11-4.06) and 4.01-fold (95% CI: 1.30-12.4) increased risk. For the replication of RANTES data in Beijing Chinese, the -28 G allele was not associated with susceptibility to SARS. However, -28 CG (OR = 4.27, 95%CI:1.64-11.1) and GG (OR = 3.34, 95%CI:0.37-30.7) were associated with admission to intensive care units or death due to SARS (P = 0.011)., Conclusion: RANTES -28 G allele plays a role in the pathogenesis of SARS.

This study evaluated the clinical and epidemiologic features of individuals with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Hong Kong from January 2004 through December 2005. Twenty-four episodes of skin and soft tissue infections and 1 episode of meningitis due to CA-MRSA were identified. CA-MRSA infections or carriage was found in 6 (13%) of 46 household contacts. A total of 29 isolates were analyzed by the Staphylococcus cassette chromosome mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing. In addition, polymerase chain reaction detection of the genes encoding Panton-Valentine leukocidin was also carried out. It was observed that 24 had SCCmec IV/IVA and 5 had SCCmec V, and 23 were pvl positive. PFGE analysis clustered all except 1 isolate into 3 pulsed-field types (PFTs), HKU100 through HKU300. The HKU100 isolates had genotype ST30-IV identical to the Southwest Pacific clone. The HKU200 isolates belonged to ST59-V and were multiresistant, including an ermB-mediated macrolide resistance trait, which is characteristic of the predominant CA-MRSA clone in Taiwan. The HKU300 isolates had unique features (ST8, Panton-Valentine leukocidin negative, and SCCmec IVA) typical of CA-MRSA in Japan. In conclusion, CA-MRSA has a propensity to spread within families. Our findings showed that CA-MRSA strains in Hong Kong have diverse genetic backgrounds.

Background: Cytokines play important roles in antiviral action. We examined whether polymorphisms of IFN-gamma,TNF-alpha and IL-10 affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS)., Methods: A case-control study was carried out in 476 Chinese SARS patients and 449 healthy controls. We tested the polymorphisms of IFN-gamma,TNF-alpha and IL-10 for their associations with SARS., Results: IFN-gamma +874A allele was associated with susceptibility to SARS in a dose-dependent manner (P < 0.001). Individuals with IFN-gamma +874 AA and AT genotype had a 5.19-fold (95% Confidence Interval [CI], 2.78-9.68) and 2.57-fold (95% CI, 1.35-4.88) increased risk of developing SARS respectively. The polymorphisms of IL-10 and TNF-alpha were not associated with SARS susceptibility., Conclusion: IFN-gamma +874A allele was shown to be a risk factor in SARS susceptibility.

In a retrospective study designed to gather information in a region with high antimicrobial resistance, the outcomes of 216 episodes of laboratory-confirmed pneumococcal bacteremia treated in Hong Kong between 1995 and 2001 were assessed. The patients had a mean age (+/-standard deviation) of 40+/-33.7 years. In all patients, the clinical diagnosis was confirmed by isolation of Streptococcus pneumoniae from blood (n=216), cerebrospinal fluid (n=7) and/or other sterile sites (n=12). Penicillin nonsusceptibility was found in 37.5% of the isolates (20.8% intermediate and 16.7% resistant). Penicillin nonsusceptibility was not a risk factor for inpatient mortality (p=0.7), nor did it affect duration of fever (p=0.4), requirement for intensive care unit admission (p=0.4) or development of suppurative complications (p=0.2). Advanced age (OR 11.3, 95%CI 4.5-28.2, p<0.01), critical illness (OR 11.3, 95%CI 4.5-28.2, p<0.001) and discordant therapy (OR 4.3, 95%CI 1.7-10.9, p<0.002) involving agents with poor anti-pneumococcal activity (but not penicillins and broad-spectrum beta-lactam agents) were significantly associated with mortality.

Background: Recently, we described the discovery of a novel group 2 coronavirus, coronavirus HKU1 (CoV-HKU1), from a patient with pneumonia. However, the clinical and molecular epidemiological features of CoV-HKU1-associated pneumonia are unknown., Methods: Prospectively collected (during a 12-month period) nasopharyngeal aspirates (NPAs) from patients with community-acquired pneumonia from 4 hospitals were subjected to reverse-transcription polymerase chain reaction, for detection of CoV-HKU1. The epidemiological, clinical, and laboratory characteristics of patients with CoV-HKU1-associated pneumonia were analyzed. The pol, spike (S), and nucleocapsid (N) genes were also sequenced., Results: NPAs from 10 (2.4%) of 418 patients with community-acquired pneumonia were found to be positive for CoV-HKU1. All 10 cases occurred in spring and winter. Nine of these patients were adults, and 4 had underlying diseases of the respiratory tract. In the 6 patients from whom serum samples were available, all had a 4-fold change in immunoglobulin (Ig) G titer and/or presence of IgM against CoV-HKU1. The 2 patients who died had significantly lower hemoglobin levels, monocyte counts, albumin levels, and oxygen saturation levels on admission and had more-extensive involvement visible on chest radiographs. Sequence analysis of the pol, S, and N genes revealed 2 genotypes of CoV-HKU1., Conclusions: CoV-HKU1 accounts for 2.4% of community-acquired pneumonia, with 2 genotypes in the study population. Without performance of diagnostic tests, the illness was clinically indistinguishable from other community-acquired pneumonia illnesses.

Two hundred non-duplicate methicillin-resistant Staphylococcus aureus (MRSA) isolates causing bacteremia in patients in four major Hong Kong hospitals during the period 2000 to 2001 were characterized by antibiogram, pulsed-field gel electrophoresis (PFGE) using SmaI restriction enzymes, and determination of staphylococcal cassette chromosome mec (SCCmec) types. Nine PFGE types, A to I, were obtained. PFGE type A constituted 50% (99/200) of all isolates and was present in isolates from all four hospitals. PFGE types A to E, had previously been identified as the major types at one of the hospitals from 1988 to 2000. The majority had a resistance profile to tetracycline (T), erythromycin (E), clindamycin (D), gentamicin (G), tobramycin (To), and ciprofloxacin (Ci), and belonged to SCCmec type III; and representatives belonged to clonal complex 239 (CC 239) (MRSA with SCCmec type III and sequence type 239, designated ST 239-MRSA-III). PFGE types F to I were new patterns that had not been previously identified in isolates from Hong Kong. PFGE type F constituted 18% (35/200) of MRSAs, had resistance profile TEGToCi, and belonged to CC 5 (ST 5-MRSA-II). PFGE type G included 13% (26/200) of MRSAs, had resistance profile TECi, and belonged to CC 45 with SCCmec type I or II. PFGE type H had characteristics similar to those of CC 239, while PFGE type I included three isolates, two of which expressed resistance to oxacillin and fusidic acid only. Two of these strains had SCCmec IVa and carried sequence type 389, with a multilocus sequence typing allelic profile of 3-35-19-2-20-26-39. Contemporary MRSAs causing bacteremia in Hong Kong hospitals belong to three clonal complexes (CC 5, CC 45, and CC 239). The most prevalent MRSA clone in Hong Kong belongs to CC 239, with PFGE types A to E and H, SCCmec type III, ST 239, and a resistance profile of TEDGToCi.

Objectives: To characterize the genetic determinants involved in the reduced susceptibility to ciprofloxacin and cefotaxime in Salmonella enterica serotype Enteritidis clinical isolates obtained from four patients in summer 2003 in Hong Kong., Methods: Three Salmonella Enteritidis isolates from blood culture and one from stool were collected due to their increased resistance to ciprofloxacin and cefotaxime. PFGE analysis was used to investigate their genetic relatedness. Conjugation experiments were employed to show if the genetic determinants involved were plasmid-mediated. MICs of various antimicrobials were determined by VITEK 2 and Etest. Based on the susceptibility and conjugation experiment results, previously described PCR methods were employed to detect sequences homologous to qnr and bla(CTX-M) suspected to be involved in the reduced susceptibility to ciprofloxacin and cefotaxime, respectively., Results: PFGE analysis showed that the four Salmonella isolates were clonally unrelated. The presence of a qnr-like gene and the CTX-M allele bla(CTX-M-14) on four different transferable plasmids harboured by the four isolates was confirmed., Conclusions: This is the first report of transferable fluoroquinolone resistance due to a new qnr allele, which appeared to be linked to bla(CTX-M-14), in isolates of Salmonella Enteritidis in Hong Kong.

Owing to the difficulties in isolating the virus and the lack of routine surveillance, the clinical significance of human parainfluenza virus 4 (HPIV-4) is less well defined than that of the other human parainfluenza viruses. We describe the first outbreak of HPIV-4 infection in a developmental disabilities unit, involving 38 institutionalized children and three staff members, during a 3-week period in autumn 2004. Most subjects had upper respiratory tract infections (URTI), while lower respiratory tract infections (LRTI) occurred in three children (7%), one complicated by respiratory failure requiring ventilation support. All patients recovered. Nasopharyngeal aspirates tested for HPIV-4 were positive by reverse transcriptase PCR (RT-PCR) in all 41 cases (100%), by direct immunofluorescence in 29 of 39 tested cases (74%), and by cell cultures in 6 of 37 cases (16%), and serum was positive for antibodies against HPIV-4 in all 35 cases (100%) with serum samples available. In addition, RT-PCR detected HPIV-4 in four children (three LRTI and one URTI) out of 115 patients with community-acquired respiratory tract infection. Molecular analysis of the 1,198-bp phosphoprotein sequences showed that HPIV-4 isolates among the cases were genetically similar, whereas the community controls were more genetically distant, supporting nosocomial transmission of a single HPIV-4 genotype during the outbreak. Moreover, the HPIV-4 causing the outbreak is more closely related to HPIV-4A than HPIV-4B. HPIV-4 may be an important cause of more severe respiratory illness in children. The present RT-PCR assay is a sensitive, specific, and rapid method for the diagnosing HPIV-4 infection. To better define the epidemiology and clinical spectrum of disease of HPIV-4 infections, HPIV-4 should be included in the routine panels of respiratory virus detection on respiratory specimens.

Objectives: To review past and present patterns of occurrence of Japanese encephalitis in Hong Kong and across Asia. A better understanding of the disease should facilitate the formulation of an effective strategic plan to prevent a future epidemic., Data Sources: Report of local cases, and literature search of MEDLINE up to November 2004., Study Selection: Literature and data related to Japanese encephalitis., Data Extraction: Relevant information and data were reviewed by the authors., Data Synthesis: Since 16 July 2004, under the ordinance of Hong Kong, Japanese encephalitis has been a notifiable disease. In the past, Japanese encephalitis has reached epidemic proportions in Japan, South Korea, and some areas in China. It has spread globally and has a worldwide incidence of 35 000 to 50 000 cases per year with 10 000 deaths. Mortality is about 30% and survivors often suffer serious long-term morbidity. In 2004, there were five local cases of Japanese encephalitis in Hong Kong. Subsequent serological surveillance of serum samples from 1547 local inhabitants revealed that 37 were positive, ie 2.4% of local inhabitants had been exposed to the Japanese encephalitis virus in the past. Most local inhabitants are immunologically naive to Japanese encephalitis virus. Most infections in endemic areas are asymptomatic. Patients with symptomatic Japanese encephalitis usually present with fever, headache, and confusion. Other signs include neurosis, poliomyelitis, and convulsion. Investigations including magnetic resonance imaging, electroencephalography, and single photon emission computed tomography are not specific. A definitive diagnosis depends on serological studies. Treatment is mainly supportive., Conclusions: The control of Japanese encephalitis in Hong Kong relies on an accurate surveillance system, vector control, vector avoidance, and vaccination of the at-risk population. At present, vaccination should be limited to travellers to endemic areas who would stay for longer than 1 month.

Little is known about the innate immune response to severe acute respiratory syndrome (SARS) coronavirus (CoV) infection. Mannose-binding lectin (MBL), a key molecule in innate immunity, functions as an ante-antibody before the specific antibody response. Here, we describe a case-control study that included 569 patients with SARS and 1188 control subjects and used in vitro assays to investigate the role that MBL plays in SARS-CoV infection. The distribution of MBL gene polymorphisms was significantly different between patients with SARS and control subjects, with a higher frequency of haplotypes associated with low or deficient serum levels of MBL in patients with SARS than in control subjects. Serum levels of MBL were also significantly lower in patients with SARS than in control subjects. There was, however, no association between MBL genotypes, which are associated with low or deficient serum levels of MBL, and mortality related to SARS. MBL could bind SARS-CoV in a dose- and calcium-dependent and mannan-inhibitable fashion in vitro, suggesting that binding is through the carbohydrate recognition domains of MBL. Furthermore, deposition of complement C4 on SARS-CoV was enhanced by MBL. Inhibition of the infectivity of SARS-CoV by MBL in fetal rhesus kidney cells (FRhK-4) was also observed. These results suggest that MBL contributes to the first-line host defense against SARS-CoV and that MBL deficiency is a susceptibility factor for acquisition of SARS.

Laribacter hongkongensis, a newly discovered bacterium recently shown to be associated with community-acquired gastroenteritis, is generally resistant to most beta-lactams except the carbapenems. We describe the cloning and characterization of a novel chromosomal class C beta-lactamase and its regulatory gene in L. hongkongensis. Two genes, ampC and ampR, were cloned by inserting restriction fragments of genomic DNA from L. hongkongensis strain HLHK5 into pBK-CMV to give the recombinant plasmid pBK-LHK-5. The ampR and ampC genes and their promoters were divergently oriented, with the ampR gene immediately upstream of the ampC gene and an intercistronic Lys-R motif, typical of inducible ampC-ampR regulatory systems. The deduced amino acid sequence of the cloned AmpC beta-lactamase (pI 8.1) contained consensus motifs characteristic of class C beta-lactamases but had identities no greater than 46% to known class C beta-lactamases. The kinetic properties of this AmpC were also compatible with those of a class C beta-lactamase. PCR of 20 clinical isolates of L. hongkongensis, including HLHK5, showed the presence of both ampC and ampR genes in all isolates. Southern hybridization suggested that the ampC gene of HLHK5 was chromosomally encoded. Subcloning experiments showed that the expression of the ampC gene of HLHK5 was regulated by its ampR gene, which acts as a repressor. The beta-lactamase characterized from strain HLHK5 was named LHK-5 (gene, bla(LHK-5)) and represents the first example of AmpC beta-lactamase in the beta subdivision of proteobacteria.

Nasopharyngeal carcinoma (NPC) is well known for its peculiarly skewed distribution with highest incidence in Southern Chinese population. Familial aggregation is evident, hence screening for early detection is offered by oncology centers in Hong Kong to first-degree relatives of patients with NPC. During the period 1994-2001, 929 family members were screened in our center. The screenees were advised to attend an annual examination that includes serological test against Epstein Barr Virus (EBV), physical examination to exclude cervical lymphadenopathy and cranial nerve palsy, and endoscopic examination of the nasopharyngeal region. Two different methods were used for the serology test: indirect immuno-fluorescent (IF) test for IgA against viral capsid antigen; and starting in 1997 enzyme-linked immunosorbent assay (ELIZA) against nuclear antigen and viral capsid antigen. Twelve cases of nasopharyngeal carcinoma were diagnosed, giving a detection rate of 5/1,155 (433/100,000) person-year for male and 7/1,404 (499/100,000) person-year for female participants observed. The corresponding average annual incidence in Hong Kong during this period was 24.1 and 9.6 per 100,000, respectively. Forty-one percent of these detected cases had Stage I disease, whereas only 2% of patients referred to the department for primary treatment presented with such early disease. Six cases were detected at first visit, and all were EBV-positive. Another 78 screenees with positive serology at first visit were followed up for 204 person years, and thus far NPC was detected in 3 after an interval of 6-32 months. Of the 845 initially EBV-negative screenees followed up for 2,337 person-years, NPC was detected in 3 after an interval of 12-45 months. One showed sero-conversion at the time of diagnosis. We conclude that family members of known patients do show a substantially higher risk of developing NPC, and regular screening by current method improves the chance of early detection., ((c) 2004 Wiley-Liss, Inc.)

Objectives: To study the effectiveness of noninvasive positive pressure ventilation (NIPPV) in the treatment of acute respiratory failure (ARF) in severe acute respiratory syndrome (SARS), and the associated infection risk., Methods: All patients with the diagnosis of probable SARS admitted to a regional hospital in Hong Kong from March 9 to April 28, 2003, and who had SARS-related respiratory distress complications were recruited for NIPPV usage. The health status of all health-care workers working in the NIPPV wards was closely monitored, and consent was obtained to check serum for coronavirus serology. Patient outcomes and the risk of SARS transmission to health-care workers were assessed., Results: NIPPV was applied to 20 patients (11 male patients) with ARF secondary to SARS. Mean age was 51.4 years, and mean acute physiology and chronic health evaluation II score was 5.35. Coronavirus serology was positive in 95% (19 of 20 patients). NIPPV was started 9.6 days (mean) from symptom onset, and mean duration of NIPPV usage was 84.3 h. Endotracheal intubation was avoided in 14 patients (70%), in whom the length of ICU stay was shorter (3.1 days vs 21.3 days, p < 0.001) and the chest radiography score within 24 h of NIPPV was lower (15.1 vs 22.5, p = 0.005) compared to intubated patients. Intubation avoidance was predicted by a marked reduction in respiratory rate (9.2 breaths/min) and supplemental oxygen requirement (3.1 L/min) within 24 h of NIPPV. Complications were few and reversible. There were no infections among the 105 health-care workers caring for the patients receiving NIPPV., Conclusions: NIPPV was effective in the treatment of ARF in the patients with SARS studied, and its use was safe for health-care workers.

We determined the susceptibilities of 265 invasive isolates of pneumococci obtained during 1995 to 2001 in Hong Kong to 11 antimicrobial agents and their serotypes. Overall, 62.6% isolates were susceptible to penicillin, 20% were intermediately resistant, and 17.4% were resistant. The overall prevalence of levofloxacin resistance (MIC > or = 8 microg/mL) was 3.8% but increased to 15.2% among the penicillin-resistant isolates. All levofloxacin-resistant isolates were clonally related; had reduced susceptibility to penicillin, cefotaxime, and clarithromycin; and were derived from adults > or = 50 years of age. Of the penicillin-nonsusceptible pneumococci, 90% from children < or = 5 years of age and 54.8% from persons of all ages were of serotypes that are included in the 7-valent pneumococcal conjugate vaccine; 93.5% from children < or = 5 years of age and 93% from persons of all ages were of serotypes that are included in the 23-valent polysaccharide vaccine.

Background: Laribacter hongkongensis has been recovered from several patients with gastroenteritis. However, the causative role of this organism in human gastroenteritis is still unproven, and sources of the bacterium are unknown. We undertook a multicentre case-control study to investigate the association of L hongkongensis with gastroenteritis., Methods: Faecal samples from patients with community-acquired gastroenteritis and controls were cultured for L hongkongensis. Targeted food surveillance was done to identify potential sources of this bacterium. All isolates of this organism from patients and food items were characterised by pulsed-field gel electrophoresis and ribotyping., Findings: During a 4-month period, L hongkongensis was recovered from 17 of 3788 patients with community-acquired gastroenteritis, but was absent in 1894 controls (p=0.001). Those who were culture-positive for this bacterium had a recent history of travel (ten [59%] patients vs two [6%] of 34 matched controls, p<0.0001), of fish consumption (16 [94%] vs 19 [56%], p=0.009), and of eating minced freshwater fish meat (five [29%] vs one [3%], p=0.012). We recovered 25 L hongkongensis isolates from intestinal samples of freshwater fish and two from minced freshwater fish meat. Bacteria with the same pulsed-field gel electrophoretic pattern and ribotype were recovered from one patient and a sample of minced freshwater fish meat, which was from the same retail market recently visited by the patient. We did not see this particular combination of electrophoretic pattern and ribotype in any other isolates., Interpretation: L hongkongensis is associated with community-acquired gastroenteritis and traveller's diarrhoea. However, its causative role has not been shown. Freshwater fish is one source of this bacterium.

Objective: There is so far no consensus on the optimal treatment strategy for the coronavirus-associated severe acute respiratory syndrome (SARS). We aimed to analyse the outcomes of a standard treatment strategy comprising antibiotics, a combination of ribavirin, a 3-week step-down course of corticosteroids, and the possibility of pulsed methylprednisolone rescue in the event of deterioration., Methodology: This was a prospective cohort study performed at a major public-funded hospital in Hong Kong. Eighty-eight World Health Organisation/Centers for Disease Control and Prevention probable cases of SARS (97% laboratory-confirmed) were treated with a standard protocol previously reported. Seventy-one patients treated de novo were analysed in detail with regard to time to clinical stabilization after combination treatment, requirement of additional therapy (pulsed methylprednisolone; assisted ventilation); and final outcomes (recovery, mortality)., Results: The mean age was 42. Twenty-one patients (24%) had comorbidities. Three of 71 treated de novo recovered with antibiotics alone. The remaining 68 received combination treatment at a mean of 5.8 days after symptom onset, of whom 30 subsequently required pulsed methylprednisolone rescue (independent predictors: older age and higher LDH) and 18 required assisted ventilation (independent predictors: older age, higher oxygen requirement and creatinine level). Their median time to clinical stabilization was 8.0 days after combination treatment (independent predictor for longer time to stabilization: median age of 41 or above). Common complications were hyperglycaemia (58%), pneumo-mediastinum/thoraces (13%), psychiatric manifestations (7%) and ventilator-associated pneumonia (2%). One patient (1%) died of SARS-related respiratory failure. All-cause mortality was 3.4%, occurring in patients aged > 65 years only. None of the discharged survivors required continuation of oxygen therapy., Conclusions: This standard treatment protocol resulted in overall satisfactory outcomes. Randomized controlled trial is suggested to confirm its efficacy.

A new selective medium, cefoperazone MacConkey agar (CMA), was developed for primary isolation of Laribacter hongkongensis from stool. Its performance in quantitative recovery and in a clinical evaluation of 4,741 human diarrheal stool specimens was superior to that of charcoal cefoperazone deoxycholate agar. In addition, with CMA, Arcobacter butzleri was unexpectedly isolated from the stools of six patients.

Aims: To define epidemiology, clinical disease, and outcome of gemella bacteraemia by 16S rRNA gene sequencing. To examine the usefulness of the Vitek, API, and ATB systems in identifying two gemella species., Methods: All alpha haemolytic streptococci other than Streptococcus pneumoniae isolated from blood cultures during a six year period were identified by conventional biochemical methods, the Vitek system, and the API system. 16S rRNA gene sequencing was performed on all isolates identified by both kits as gemella with >or= 95% confidence or by either kit as any bacterial species with < 95% confidence. The ATB expression system was used to identify the two isolates that were defined as gemella species by 16S rRNA gene sequencing., Results: Of the 302 alpha haemolytic streptococci other than S pneumoniae isolated, one was identified as Gemella morbillorum, and another as Gemella haemolysans by 16S rRNA gene sequencing. The patient with monomicrobial G morbillorum bacteraemia was a 66 year old man with community acquired infective endocarditis with septic thromboemboli. The patient with G haemolysans bacteraemia was a 41 year old woman with hospital acquired polymicrobial bacteraemia during the neutropenic period of an autologous bone marrow transplant for non-Hodgkin's lymphoma, the first case of its kind in the English literature. The API and ATB expression systems only identified the second strain as G haemolysans at 94% and 99% confidence, respectively, whereas the Vitek system identified none of the two strains correctly at > 70% confidence., Conclusions: Gemella bacteraemia is uncommon. 16S rRNA gene sequencing is the method of choice for identification of gemella and gemella-like isolates.

Phenotypic identification of fungi in clinical microbiology laboratories is often difficult and late, especially for slow growing and rarely encountered fungi. We describe the application of 18S ribosomal RNA (rRNA) gene sequencing in the early diagnosis of a case of Exophiala peritonitis. A yeast-like fungus was isolated from the dialysate fluid of a 66-year-old man undergoing continuous ambulatory peritoneal dialysis. It grew slowly after 12 days of incubation to yield mature cultures to permit recognition of microscopic features resembling those of Exophiala, a dematiacerous mold. 18S rRNA gene sequencing provided results 12 days earlier than phenotypic identification and revealed 15 base difference (0.9%) between the isolate and Exophiala sp. strain GHP 1205 (GenBank Accession no. AJ232954), indicating that the isolate most closely resembles a strain of Exophiala species. The patient responded to 4 weeks of intravenous amphotericin B therapy. Early identification of the fungus was important for the choice of anti-fungal regimen. As opportunistic fungal infections in immunocompromised patients are globally emerging problems, the development of molecular techniques for fungal identification is crucial for early diagnosis and appropriate treatment.

A series of 31 patients with probable SARS, diagnosed from WHO criteria, were treated according to a treatment protocol consisting of antibacterials and a combination of ribavirin and methylprednisolone. Through experience with the first 11 patients, we were able to finalise standard dose regimens, including pulsed methylprednisolone. One patient recovered on antibacterial treatment alone, 17 showed rapid and sustained responses, and 13 achieved improvement with step-up or pulsed methylprednisolone. Four patients required short periods of non-invasive ventilation. No patient required intubation or mechanical ventilation. There was no mortality or treatment morbidity in this series.

We did a case-control study in five Hong Kong hospitals, with 241 non-infected and 13 infected staff with documented exposures to 11 index patients with severe acute respiratory syndrome (SARS) during patient care. All participants were surveyed about use of mask, gloves, gowns, and hand-washing, as recommended under droplets and contact precautions when caring for index patients with SARS. 69 staff who reported use of all four measures were not infected, whereas all infected staff had omitted at least one measure (p=0.0224). Fewer staff who wore masks (p=0.0001), gowns (p=0.006), and washed their hands (p=0.047) became infected compared with those who didn't, but stepwise logistic regression was significant only for masks (p=0.011). Practice of droplets precaution and contact precaution is adequate in significantly reducing the risk of infection after exposures to patients with SARS. The protective role of the mask suggests that in hospitals, infection is transmitted by droplets.

The aim of this study was to assess the clinical spectrum of peripartum tuberculosis from the perspective of immunorestitution disease. Of 29 patients with peripartum tuberculosis, 27 (93.1%) had extrapulmonary tuberculosis, 20 (69%) of whom were affected in the central nervous system. Twenty-two (75.9%) patients had no clinical features suggestive of tuberculosis during pregnancy. The median time from delivery to the onset of immunorestitution was 4 days, but treatment with anti-tuberculous therapy was delayed for a median time of 27 days after the onset of symptoms. Despite therapy, 11 (38%) patients died and 4 (13.8%) had residual functional deficits. Peripartum tuberculosis is an important differential diagnosis of postpartum fever (of unknown origin) without localized signs.

Background: An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients., Methods: We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked., Findings: Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus., Interpretation: A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.

Traditionally, the identification, epidemiology and spectrum of clinical diseases caused by Granulicatella adiacens and Abiotrophia defectiva are dependent upon their phenotypic characterization. During a 6-year period (July 1995-June 2001), seven and two alpha-haemolytic streptococci were identified as G. adiacens and A. defectiva, respectively, by 16S rRNA gene sequencing. Three patients with haematological malignancies and neutropenic fever had primary bacteraemia. Three patients with valvular problems or congenital heart disease had infective endocarditis. A patient with ischemic heart disease and cerebrovascular accident had infected aortic atheroma with dissection. A patient with recurrent pyogenic cholangitis had acute cholangitis and a patient with polypoid cystitis and benign prostatic hypertrophy had acute prostatitis. Four of the nine patients died, including all three with G. adiacens infective endocarditis or infected atheroma. For the seven G. adiacens isolates, the API 20 STREP system successfully identified one and five isolates as G. adiacens with >95 % and 80-90 % confidence, respectively, whereas the Vitek System (GPI) and ATB Expression system (ID32 STREP) successfully identified none and one isolate as G. adiacens. Of the two A. defectiva isolates, none of the three systems successfully identified either of them as A. defectiva. 16S rRNA gene sequencing is the technique of choice for identifying G. adiacens and A. defectiva, and early surgical intervention should be considered when G. adiacens endocarditis is diagnosed.

Analysis of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) isolates in Hong Kong by use of a combination of antibiogram typing, serotyping, multilocus sequence typing, and pulsed-field gel electrophoresis indicated that the dissemination of PNSP was the result of the spread of international clones: variants of the Spain(23F)-1 or Spain(6B)-2 clones were the predominant PNSP isolates from 1994 to 1997 and remained so, but Taiwan(19F)-14 and Taiwan serotype 6B clones were disseminated in Hong Kong in 1999 and 2000. Concomitant changes in antibiotic susceptibility profiles, with the rate of susceptibility to chloramphenicol rising from 10% in the period from 1994 to 1997 to 31% (P < 0.001) in 1999 and 2000, were noted to accompany the shift of clones.

The MICs of 13 antimicrobial agents including seven fluoroquinolones (ciprofloxacin, levofloxacin, sparfloxacin, grepafloxacin, gatifloxacin, moxifloxacin and clinafloxacin) for Streptococcus pneumoniae isolates obtained from all regions of Hong Kong in the year 2000 were determined by the Etest. Overall, 39.4% of 180 isolates were susceptible to penicillin, 11.7% were intermediate and 48.9% were resistant. The overall prevalence of fluoroquinolone non-susceptibility (levofloxacin MIC > or = 4 mg/L) was 13.3% but increased to 27.3% among the penicillin-resistant isolates. For the fluoroquinolone non-susceptible isolates, within-class cross-resistance was common. For the fluoroquinolone non-susceptible isolates, the median MICs of clinafloxacin, gatifloxacin, moxifloxacin, sparfloxacin and grepafloxacin were, respectively, six-, 24-, 32- 84- and 128-fold higher than those for the susceptible isolates. All fluoroquinolone non-susceptible strains were derived from adults. The prevalence of fluoroquinolone resistance was higher in isolates from older patients (17.1% among those > or = 65 years of age versus 9.1% among those 18-64 years of age, P < 0.001) and from adults with chronic obstructive pulmonary disease (24.6% versus 9.3%, P = 0.01). All fluoroquinolone non-susceptible strains were non-susceptible to penicillin (MIC range 2-4 mg/L), cefotaxime (MIC range 1-4 mg/L) and erythromycin (MIC range 4- > or = 256 mg/L). The fluoroquinolone non-susceptible isolates were genetically related to the Spain(23F)-1 clone when analysed by pulse-field gel electrophoresis and multilocus sequence typing. In conclusion, a rapid increase in the prevalence of fluoroquinolone resistance among S. pneumoniae was found in Hong Kong. Typing analysis suggests that this is due to the pan-regional dissemination of a fluoroquinolone-resistant variant (designated Hong Kong(23F)-1) of the globally distributed Spain(23)F-1 clone.

Erythromycin resistance rates among penicillin-susceptible Streptococcus pneumoniae were 38 and 92% among penicillin-intermediate and -resistant S. pneumoniae isolates from Hong Kong, respectively, and 27% (43 of 158) of the isolates showed the MLS(B) phenotype, and the majority carried the ermB gene; 73% (115 of 158) displayed the M phenotype, and all possessed the mef gene. The MLS(B) phenotype was predominant in penicillin-susceptible, macrolide-resistant isolates and in penicillin-nonsusceptible isolates of serotype 6B, whilst the M phenotype was predominant in penicillin-intermediate or -resistant isolates belonging to serotype 23F or 19F. Extensive spread of clones of drug-resistant pneumococci has led to the widespread presence of macrolide resistance in S. pneumoniae in Hong Kong.

The relationship between the phenotypic and genotypic characteristics of 105 penicillin-intermediate or -resistant Streptococcus pneumoniae isolates saved during 1994 to 1997 at the Prince of Wales Hospital and Pamela Youde Nethersole Eastern Hospital, Hong Kong, was studied. The pbp genes for penicillin-binding proteins 1a, 2b, and 2x for each isolate were amplified by PCR, and the products were digested with restriction enzymes HinfI and AluI. A combination of the pulsed-field gel electrophoresis (PFGE) profiles, pbp fingerprints, and phenotypic characteristics of capsular types and antibiograms enabled these isolates to be divided into four major groups. Seventy-four percent (78 of 105) of the strains, belonging to serotypes 23F, 19F, and 14, showed indistinguishable pbp fingerprint patterns (group A1, 1-1-1, 1-1-1), with PFGE patterns belonging to group A and its subtypes, suggesting that these strains were closely related. Eighty-three percent (65 of 78) of these isolates were also resistant to tetracycline, erythromycin, chloramphenicol, and trimethoprim. The type 23F isolates were indistinguishable from representative strains of the Spanish 23F clone by these molecular methods, indicating that these strains may be variants of the Spanish 23F clone. Serotype 6B accounted for 19% (20 of 105) of the isolates with reduced penicillin susceptibility and was made up of variants belonging to four different pbp fingerprint groups with the PFGE pattern group B, the predominant group being indistinguishable from that of the Spanish 6B clone. Other PFGE and fingerprint groups were mainly obtained from penicillin-susceptible strains of various serotypes. The results suggest that the rapid emergence of drug-resistant S. pneumoniae in Hong Kong has been due to the rapid dissemination of several successful clones.

Background: A study was conducted to evaluate the prevalence of metronidazole resistant Helicobacter pylori strains among the Chinese in Hong Kong. The efficacy of the triple therapy that contains metronidazole as one of the anti-microbial agents in eradication of the metronidazole susceptible and the metronidazole resistant strains was also assessed., Methods: Culture for H pylori was attempted from antral biopsy specimens of 70 peptic ulcer and 51 control subjects. Successfully cultured H pylori strains were tested for metronidazole susceptibility. Twenty six peptic ulcer disease subjects who had received a course of triple therapy were also reassessed four to six weeks later for successful eradication of H pylori infection., Results and Conclusions: H pylori was successfully cultured from antral biopsy specimens in 69 of 80 (86%) of the infected subjects. The overall metronidazole resistance rate was 53.5% (37 of 69). There was a significantly higher metronidazole resistance rate among H pylori isolates from the asymptomatic controls (20 of 25) than the peptic ulcer disease subjects (17 of 44) (p = 0.0007). Twenty three of 32 (73%) women and 14 of 37 (38%) men harboured the metronidazole resistant strains. There was no sex or age difference as far as the prevalence of metronidazole resistant strains were concerned within each study group. Pre-treatment metronidazole susceptible H pylori were significantly more likely to respond to the triple therapy used than those with the metronidazole resistant ones (14 of 15 v five of 10) (p = 0.021).

Over a five-year period, 125 newborns with necrotizing enterocolitis (NEC) were managed by us. Their mean birthweight was 1700 g and mean maturity was 32 weeks. Before commencement of antibiotics, routine septic work-up was done in order to define the bacterial spectrum and antibiotic sensitivity. The study includes aerobic and anaerobic cultures of gastric and pharyngeal aspirates, blood cultures, umbilical swabs and culture of umbilical catheter tips in relevant cases. Peritoneal swab results were also analyzed if laparatomy was performed. Positive cultures were present in 45 patients (36%) with 55 positive specimens. Fifteen types of organism were isolated: the commonest was Enterobacter (29%), followed by E. coli (14.5%) and Klebsiella (13%). They were resistant to ampicillin and first-generation cephalosporin. These organisms were usually opportunistic pathogens. Overgrowth of them may be the cause of NEC. Regular review of the antibiotic sensitivity of these organisms allows prompt and appropriate choice of antibiotics. At the same time, antibiotic sensitivity for these organisms was analyzed to guide us in the choice of antibiotic therapy.

Among 27 cases of Pseudomonas septicaemia in the Department of Paediatrics of Queen Mary Hospital from 1981 to 1988, we have identified 10 children without known predisposing causes before presentation and report their clinical features. Six were infants, of whom 4 developed shock on admission and died. Ecthyma gangrenosum was present in 4 patients. Pseudomonas aeruginosa was isolated in 8 patients. All isolates, except Ps. cepacia, were sensitive to gentamicin. One patient had cyclical neutropenia. Another had an appendicular abscess. Salmonella was cultured from the stool in one patient. Although Pseudomonas septicaemia is normally considered to be associated with underlying immunodeficiency, in 22% it occurred in previously healthy children. Mortality is high especially in infants who develop septicaemic shock. It is advisable to cover for Pseudomonas septicaemia with aminoglycosides or ceftazidime in sick septic infants.

The efficacy of ofloxacin in preventing infection in neutropenic patients following cytotoxic chemotherapy was evaluated and was compared with that of co-trimoxazole. A total of 102 patients with hematological malignancies were randomly selected to receive either co-trimoxazole or ofloxacin. All patients were monitored for compliance, occurrence of infection, and drug-related side effects. A surveillance culture of a rectal swab was performed regularly. A total of 25 of the 52 patients (48%) who received co-trimoxazole and 11 of the 50 patients (22%) who received ofloxacin developed fever during the study period (P less than 0.025). Gram-negative bacteremia occurred in nine patients in the co-trimoxazole group (17%) but in only one patient (2%) in the ofloxacin group (P less than 0.05). No patient in either group had documented gram-positive bacterial or Pneumocystis carinii infection. Poor performance status was the only identifiable factor associated with an increased incidence of bacteremia. The surveillance study showed that significantly fewer bacterial strains were resistant to ofloxacin than to co-trimoxazole and that acquisition of resistance to co-trimoxazole was more commonly observed than was acquisition of resistance to ofloxacin. Significantly more patients had skin rashes following co-trimoxazole than ofloxacin treatment (P less than 0.05). Ofloxacin was superior to co-trimoxazole in preventing infection in this population of neutropenic patients.

Recurrent aseptic meningitis of Mollaret is a rare condition. We report a Chinese patient with Mollaret's meningitis and describe the characteristic cytological changes in the cerebrospinal fluid. The diagnosis and treatment of this condition is discussed with a review of the English literature.