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Background The magnitude and risk factors of progression of atherosclerosis in Asian HIV-infected individuals were unknown. This study aimed to evaluate: (1) the rate of progression of atherosclerosis in HIV-infected individuals, and (2) metabolic and inflammatory parameters that may predict atherosclerosis progression in HIV-infected individuals in an Asian cohort. Setting A prospective, longitudinal study was performed among adults attending an HIV Metabolic clinic in Hong Kong. Methods Carotid intima media thickness (cIMT) was measured at baseline and 24 months. Body composition, metabolic, and inflammatory biomarkers [including homeostasis model assessment of insulin resistance, LDL (low-density lipoprotein) cholesterol particle size, high-sensitive C reactive protein, adiponectin] associated with cIMT change were analyzed; their predictive performances were estimated using receiver operating characteristic analyses. Results Sixty-one HIV-infected individuals (mean ± SD age 49.8 ± 11.4 years, 89% men, 97% Chinese, diabetes 39%, hypertension 30%, and dyslipidemia 85%) were recruited. Annual rate of change of cIMT was +0.0075 (0.0000-0.0163) mm/yr, and 19% developed new plaque at 24 months. Two patients died during the study period, 1 because of sudden cardiac death. Using receiver operating characteristic analyses, combination of lower limb fat percentage, LDL cholesterol subclass pattern B, and lower adiponectin level, but not Framingham score, predicted greater cIMT progression in HIV-infected individuals. Conclusions Asian HIV-infected individuals had atherosclerosis progression. Limb fat percentage, LDL cholesterol particle size, and adiponectin level may identify at-risk Asian HIV-infected individuals for early intervention.

We aimed to describe disease burden, characteristics, and outcomes of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) in Hong Kong. A retrospective, observational study was conducted in 26 Hong Kong public hospitals between January 2010 and December 2012. The primary outcome measures were 30-day mortality rate and infection-related hospital cost. Of 1133 patients reviewed, 727 (64.17%) were male, 1075 (94.88%) had health care-associated community-onset and 44 (3.88%) had hospital-onset MRSA infection. The mean age of patients was 76 (SD = 15) years, including 172 (15.18%) aged 20 to 59 years and 961 (84.8%) aged ≥60 years. The annual incidence rates in age groups of 20 to 59 years and ≥60 years were 0.96 to 1.148 per 100 000 and 22.7 to 24.8 per 100 000, respectively. The 30-day mortality was 367 (32.39%). Older patients (79 years), chronic lung disease, and prior hospitalization were associated with increased mortality. The mean cost was US$10 565 (SD = 11 649; US$1 = HK$7.8). MRSA BSI was a significant burden in Hong Kong.

Introduction − Macrolides can ameliorate inflammation in respiratory diseases, providing clinical benefits. Data in influenza is lacking. Method − A randomized, open-label, multicenter trial among adults hospitalized for laboratory-confirmed influenza was conducted. Study treatments of oseltamivir and azithromycin (500 mg/day), or oseltamivir alone, both for 5 days, were allocated at 1:1 ratio. The primary outcome was plasma cytokine/chemokine concentration change over time (Day 0–10); secondary outcomes were viral load and symptom score changes. Generalized Estimating Equation (GEE) models were used to analyze longitudinal data. Results − Fifty patients were randomized to the oseltamivir-azithromycin or oseltamivir groups, with comparable baseline characteristics (age, 57 ± 18 years; A/H3N2, 70%), complications (72%), and viral load. Pro-inflammatory cytokines IL-6 (GEE: β −0.037, 95%CI-0.067,-0.007, P = 0.016; reduction from baseline −83.4% vs −59.5%), CXCL8/IL-8 (β −0.018, 95%CI-0.037,0.000, P = 0.056; −80.5% vs −58.0%), IL-17 (β −0.064, 95%CI-0.117,-0.012, P = 0.015; −74.0% vs −34.3%), CXCL9/MIG (β −0.010, 95%CI-0.020,0.000, P = 0.043; −71.3% vs −56.0%), sTNFR-1, IL-18, and CRP declined faster in the oseltamivir-azithromycin group. There was a trend toward faster symptom resolution (β −0.463, 95%CI-1.297,0.371). Viral RNA decline (P = 0.777) and culture-negativity rates were unaffected. Additional ex vivo studies confirmed reduced induction of IL-6 (P = 0.017) and CXCL8/IL-8 (P = 0.005) with azithromycin. Conclusion − We found significant anti-inflammatory effects with adjunctive macrolide treatment in adults with severe influenza infections. Virus control was unimpaired. Clinical benefits of a macrolide-containing regimen deserve further study. [ClinicalTrials.gov NCT01779570]

Objective.To determine the prevalence, risk factors, and molecular epidemiology of methicillin-resistantStaphylococcus aureus(MRSA) colonization at the time of admission to acute medical units and to develop a cost-effective screening strategy.Methods.Nasal and groin screening cultures were performed for patients at admission to 15 acute medical units in all 7 catchment regions in Hong Kong. All MRSA isolates were subjected tospatyping.Results.The overall carriage rate of MRSA was 14.3% (95% confidence interval [CI], 13.5–15.1). MRSA history within the past 12 months (adjusted odds ratio [OR], 4.60 [95% CI, 3.28–6.44]), old age home residence (adjusted OR, 3.32 [95% CI, 2.78–3.98]), and bedbound state (adjusted OR, 2.19 [95% CI, 1.75–2.74]) were risk factors selected as MRSA screening criteria that provided reasonable sensitivity (67.4%) and specificity (81.8%), with an affordable burden (25.2%).spatyping showed that 89.5% (848/948) of the isolates were clustered into the 4spaclonal complexes (CCs):spaCC1081,spaCC032,spaCC002, andspaCC4677. Patients colonized with MRSAspatypes t1081 (OR, 1.77 [95% CI, 1.49–2.09]) and t4677 (OR, 3.09 [95% CI, 1.54–6.02]) were more likely to be old age home residents.Conclusions.MRSA carriage at admission to acute medical units was prevalent in Hong Kong. Our results suggest that targeted screening is a pragmatic approach to increase the detection of the MRSA reservoir. Molecular typing suggests that old age homes are epicenters in amplifying the MRSA burden in acute hospitals. Enhancement of infection control measures in old age homes is important for the control of MRSA in hospitals.

Background. Better understanding of complications and outcomes of adults hospitalized with respiratory syn-cytial virus (RSV) infection is necessary.Methods. A retrospective cohort study was conducted on all adults (≥18 years) admitted to 3 acute care generalhospitals in Hong Kong with virologically confirmed RSV infection during 2009–2011 (N=607). Adults hospital-ized forseasonal influenza during the period wereused forcomparison (n=547). Both infections were prospectivelydiagnosed following a standard protocol. Independent reviews of chest radiographs were performed by radiologists.Main outcome measures were all-cause death, respiratory failure requiring ventilatory support, and hospitalizationduration. Cox proportional hazards models were used foranalyses.Results. Themeanage ofRSV patients was75 (SD,16) years; 87% hadunderlyingconditions. Lower respiratoryand cardiovascularcomplications were diagnosed in 71.9% (pneumonia, 42.3%; acute bronchitis, 21.9%; chronic ob-structive pulmonary disease/asthma exacerbation, 27.3%) and 14.3% of patients, respectively; 12.5% had bacterialsuperinfections. Supplemental oxygen and ventilatory support were required in 67.9% and 11.1%, respectively.Crude all-cause mortality was 9.1% and 11.9% within 30days and 60 days, respectively; mean length ofstayof survi-vors was 12 (SD, 13) days. Advanced age, radiographic pneumonia, requirement for ventilation, bacterial superin-fection, and elevated urea level and white blood cell count were independently associated with poorer survival.Systemic corticosteroid use was associated with longer hospitalization and secondary infections. The overall out-comes of survival and length of stay were not significantly different from those in influenza.Conclusions. RSV can cause severe lower respiratory complications in older adults, resulting in respiratoryfailure, prolonged hospitalization, and high mortality similar to seasonal influenza. Corticosteroids did not seem toimprove outcomes. The unmet need forantiviral therapy and vaccination against RSV in adults should be promptlyaddressed.Keywords. RSV; hospitalization; respiratory failure; lower respiratory tract infection; adults.Respiratory syncytial virus (RSV) is known to be animportant cause of lower respiratory tract infection ininfants and young children, leading to hospitalizationsand deaths [1]. Its impact in adults, however, has onlybeen appreciated in recent years. It has been estimatedthat RSV infects 3%–10% of adults annually; althoughmost infections are mild, increasing evidence suggeststhat severe lower respiratory tract infections can occur,especially among older adults and those with underlyingconditions [2–4].RSV may have accounted for 5%–15%of community-acquired pneumonia, 9%–10% of hospi-tal admissions for acute cardiorespiratory diseases, andexcessive deaths duringseasonalpeaks [3,4].Thedisease

Background Beginning from late 2011 and early 2012, increasing circulation of antigenically drifted influenza A/Victoria/361/2011-like H3N2 viruses within genotype 3 of the A/Victoria/208/2009 clade have been reported in multiple European countries and elsewhere. Whether these emerging viruses are associated with increased disease severity is unclear. Objectives To report the clinical and virological findings of a moderately severe hospital outbreak of A/Victoria/361/2011-like viruses that occurred in November 2011 in Hong Kong. Study design Clinical and virological hospital outbreak investigation. Results The outbreak occurred in an adult psychiatric ward in November 2011, a time well before the usual local seasonal influenza winter peak. Altogether, 7 patients and 1 healthcare-worker were affected (mean age, 47 [range, 34–61] years). The attack rates among patients and healthcare-workers were 33% (7/21) and 7% (1/15), respectively. Pneumonia developed in 38% (3/8) of cases; none had underlying immunocompromised conditions. High nasopharyngeal viral loads were detected. All cases responded to antiviral treatment. Multiple amino acid mutations with reference to earlier A(H3N2) vaccine strains were mapped to key antigenic sites on hemagglutinin; however, no critical mutations on receptor binding sites were detected. Viral sequence variations jeopardized the performance of molecular diagnostic assays. Conclusions Severe disease and pneumonia occurred in a substantial proportion of non-immunocompromised adults in a hospital outbreak attributed to the emerging antigenically drifted A/Victoria/361/2011-like H3N2 viruses. Close monitoring of the transmission of this drift variant is required. Further studies are also necessary to determine virus virulence.

Background We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1) / Receptor-for-Advanced-Glycation-End-products (RAGE) signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB). Methods A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80); age-and-sex matched asymptomatic individuals (tested for latent TB) were used for comparison (n = 45). Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA) of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients’ PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan) for cytokine induction ex vivo. Results In active PTB, plasma IL-8/CXCL8 [median(IQR), 6.0(3.6–15.1) vs 3.6(3.6–3.6) pg/ml, P

It is unclear whether pandemic 2009 influenza A (pH1N1) infection caused more significant disease among hospitalized adults than seasonal influenza.A prospective, observational study was conducted in adults hospitalized with polymerase chain reaction-confirmed pH1N1 infection in 2 acute-care general hospitals from June 2009 to May 2010 (n = 382). Complications and outcomes were described and compared with those in a seasonal influenza cohort (2007-2008, same hospitals; n = 754).Hospitalized patients with pH1N1 influenza were younger than those with seasonal influenza (mean age ± standard deviation, 47 ± 20 vs 70 ± 19 years) and fewer had comorbid conditions (48% vs 64%). The rate of positive immunofluorescence assay results was low (54% vs 84%), and antiviral use was frequent (96% vs 52%). Most patients in both cohorts developed complicated illnesses (67.8% vs 77.1%), but patients with pH1N1 influenza had higher rates of extrapulmonary complications (23% vs 16%; P = .004) and intensive care unit admission and/or death (patient age35 years, 2.3% vs 0%; 35-65 years, 12.4% vs 3.2%;65 years, 13.5% vs 8.5%; adjusted odds ratio [OR] 2.13; 95% confidence interval [CI], 1.25-3.62; P = .005). Patients who received antiviral treatment within 96 h after onset had better survival (log-rank test, P.001). However, without timely treatment, the mortality risk was higher with pH1N1 infection (9.0% vs 5.8% for seasonal influenza; adjusted OR, 6.85; 95% CI, 1.64-28.65; P = .008]. Bacterial superinfection worsened outcomes.Adults hospitalized for pH1N1 influenza had significant complications and mortality despite being younger than patients with seasonal influenza. Antiviral treatment within 96 h may improve survival.

BACKGROUND: We examined the role of aerosol transmission of influenza in an acute ward setting. METHODS: We investigated a seasonal influenza A outbreak that occurred in our general medical ward (with open bay ward layout) in 2008. Clinical and epidemiological information was collected in real time during the outbreak. Spatiotemporal analysis was performed to estimate the infection risk among patients. Airflow measurements were conducted, and concentrations of hypothetical virus-laden aerosols at different ward locations were estimated using computational fluid dynamics modeling. RESULTS: Nine inpatients were infected with an identical strain of influenza A/H3N2 virus. With reference to the index patient's location, the attack rate was 20.0% and 22.2% in the "same" and "adjacent" bays, respectively, but 0% in the "distant" bay (P = .04). Temporally, the risk of being infected was highest on the day when noninvasive ventilation was used in the index patient; multivariate logistic regression revealed an odds ratio of 14.9 (95% confidence interval, 1.7-131.3; P = .015). A simultaneous, directional indoor airflow blown from the "same" bay toward the "adjacent" bay was found; it was inadvertently created by an unopposed air jet from a separate air purifier placed next to the index patient's bed. Computational fluid dynamics modeling revealed that the dispersal pattern of aerosols originated from the index patient coincided with the bed locations of affected patients. CONCLUSIONS: Our findings suggest a possible role of aerosol transmission of influenza in an acute ward setting. Source and engineering controls, such as avoiding aerosol generation and improving ventilation design, may warrant consideration to prevent nosocomial outbreaks.

BackgroundThe goal of this study was to characterize viral loads and factors affecting viral clearance in persons with severe influenza MethodsThis was a 1-year prospective, observational study involving consecutive adults hospitalized with influenza. Nasal and throat swabs were collected at presentation, then daily until 1 week after symptom onset. Real-time reverse-transcriptase polymerase chain reaction to determine viral RNA concentration and virus isolation were performed. Viral RNA concentration was analyzed using multiple linear or logistic regressions or mixed-effect models ResultsOne hundred forty-seven inpatients with influenza A (H3N2) infection were studied (mean age ± standard deviation, 72±16 years). Viral RNA concentration at presentation positively correlated with symptom scores and was significantly higher than that among time-matched outpatients (control subjects). Patients with major comorbidities had high viral RNA concentration even when presenting >2 days after symptom onset (mean ± standard deviation, 5.06±1.85 vs 3.62±2.13 log10 copies/mL; P=.005; β, +0.86 [95% confidence interval, +0.03 to +1.68]). Viral RNA concentration demonstrated a nonlinear decrease with time; 26% of oseltamivir-treated and 57% of untreated patients had RNA detected at 1 week after symptom onset. Oseltamivir started on or before symptom day 4 was independently associated with an accelerated decrease in viral RNA concentration (mean β [standard error], −1.19 [0.43] and −0.68 [0.33] log10 copies/mL for patients treated on day 1 and days 2–3, respectively; P

Purpose To determine whether the initial chest radiograph is helpful in predicting the clinical outcome of patients with severe acute respiratory syndrome (SARS). Methods Of 343 patients who met the World Health Organization's case definition of probable SARS and who had been admitted to a regional hospital in Hong Kong, 201 patients had laboratory evidence of SARS coronavirus infection. The initial frontal chest radiographs of these 201 patients were assessed in a blinded fashion by 3 radiologists; individual findings were accepted if at least 2 of the radiologists concurred. Independent predictors of an adverse outcome, defined as the need for assisted ventilation, death, or both, were identified by multivariate analysis. Results Bilateral disease and involvement of more than two zones on the initial chest radiograph were associated with a higher risk of liver impairment and poor clinical outcome. Forty-two patients (21%) developed an adverse outcome. Multivariate analysis showed that lung involvement of more than two zones (odds ratio [OR] = 7.0; 95% confidence interval [CI]: 2.7 to 17.9), older age (OR for each decade of life=1.5; 95% CI: 1.1 to 2.0), and shortness of breath on admission (OR = 2.8; 95% CI: 1.1 to 7.4) were independent predictors of an adverse outcome. Conclusion Frontal chest radiographs on presentation may have prognostic value in patients with SARS.

Liver impairment is commonly reported in up to 60% of patients who suffer from severe acute respiratory syndrome (SARS). Here we report the clinical course and liver pathology in three SARS patients with liver impairment. Three patients who fulfilled the World Health Organization case definition of probable SARS and developed marked elevation of alanine aminotransferase were included. Percutaneous liver biopsies were performed. Liver specimens were examined by light and electron microscopy, and immunohistochemistry. Reverse‐transcriptase polymerase chain reaction (RT‐PCR) using enhanced real‐time PCR was applied to look for evidence of SARS‐associated coronavirus infection. Marked accumulation of cells in mitosis was observed in two patients and apoptosis was observed in all three patients. Other common pathologic features included ballooning of hepatocytes and mild to moderate lobular lymphocytic infiltration. No eosinophilic infiltration, granuloma, cholestasis, fibrosis, or fibrin deposition was noted. Immunohistochemical studies revealed 0.5% to 11.4% of nuclei were positive for proliferative antigen Ki‐67. RT‐PCR showed evidence of SARS‐associated coronavirus in the liver tissues, but not in the sera of all 3 patients. However, electron microscopy could not identify viral particles. No giant mitochondria, micro‐ or macro‐vesicular steatosis was observed. In conclusion, hepatic impairment in patients with SARS is due to SARS‐associated coronavirus infection of the liver. The prominence of mitotic activity of hepatocytes is unique and may be due to a hyperproliferative state with or without disruption of cell cycle by the coronavirus. With better knowledge of pathogenesis, specific therapy may be targeted to reduce viral replication and modify the disease course. (Hepatology 2004;39:302–310.)

Fecal viral concentrations of 40 patients infected with norovirus genogroup GII.4 correlated with diarrhea duration and frequency of vomiting. Higher viral concentration and older age were independently associated with prolonged diarrhea (> or =4 days). These findings provide information on the pathogenesis and transmission of norovirus infections.

Background Little is known about the virological and inflammatory responses of severe pandemic 2009 influenza A(H1N1) virus pneumonia during antiviral treatment. Methods In a prospective observational study, we recruited consecutive adults hospitalized with confirmed pandemic 2009 H1N1 infection during a 16-week period. Nasopharyngeal aspirate and non-respiratory samples (blood, stool and urine) were collected at presentation, and serial nasopharyngeal flocked swabs (NPFS) and tracheal aspirates (TA) were collected after initiating oseltamivir treatment for quantitative viral RNA assay, using real-time reverse transcriptase-PCR. Serial plasma samples were collected for cytokine/chemokine assay using cytometric bead array. Patients with severe pneumonia (lung infiltrates and hypoxaemia) were compared to those with milder illnesses. Results A total of 66 patients were studied (mean age 43 ±20 years); 28 (42%) developed severe pneumonia, of whom 10 (15%) required intubation. Severe pneumonia was associated with older age, dyspnoea, delayed presentation >2 days from onset, extrapulmonary virus detection (13–28%) and higher viral concentration despite late-presentation (multiple linear regression, β=0.94, 95% confidence interval 0.15–1.74; P=0.02). Patients with severe pneumonia exhibited slow viral clearance with oseltamivir treatment, particularly in the lower respiratory tract (median [interquartile range] durations of RNA positivity after antiviral initiation were NPFS 6.0 days [3.0–8.0], TA 11.0 days [7.8–14.3] versus milder illness group NPFS of 2.0 days [1.0–3.0] days; PConclusions In severe 2009 H1N1 pneumonia, viral clearance is slow with treatment, particularly in the lower respiratory tract. A more sustained antiviral regime appears warranted.

Summary Objectives Early diagnosis of smear-negative tuberculosis remains challenging. The role of an interferon-gamma release assay (IGRA) in discriminating active pulmonary tuberculosis (PTB) among cases of ‘pneumonia' was investigated. Methods Consecutive patients admitted to an acute hospital in Hong Kong (intermediate TB burden) during 2006–2008 because of pneumonia and suspected PTB were recruited for IGRA (Quantiferon-TB Gold, QFN-G) study. Diagnosis of tuberculosis was confirmed by mycobacterial culture or histology. Results Altogether 179 patients were recruited (median (IQR) age 59 (44–75), 68.7% male); active PTB was confirmed in 63 (35.2%). Among the AFB-smear-negative ‘pneumonias' ( n = 152), age>50 (OR 0.27, 95% CI 0.09–0.84), absence of weight loss (OR 0.30, 95% CI 0.10–0.88), and negative IGRA (OR 0.08, 95% CI 0.03–0.25) were independently associated with lower risks of PTB. The overall sensitivity, specificity, positive and negative predictive values for the IGRA in diagnosing active PTB were 60%, 87%, 72% and 80% respectively. Among smear-negative ‘pneumonias' ( n = 152), the performance values of IGRA were 64%, 87%, 62% and 88% respectively; in the absence of characteristic clinical or radiographic features of PTB, the negative predictive value (NPV) improved to 90–95%. Conclusions The high NPV of QFN-G among smear-negative ‘pneumonias' can be useful for risk stratification in hospitalized patients suspected of PTB. Further investigation on the role of these assays in patient management is warranted.

Background Aspartic acid to glycine substitution (D222G) of haemagglutinin subunit (HA1) was associated with adverse outcomes in 2009 pandemic influenza A (H1N1) infections. Objectives To characterize the virological profile and antiviral response of patients infected with the HA1 D222G mutant. Study design Sixty-three adults admitted for pandemic influenza in Hong Kong were tested for D222G mutation by direct sequencing. Nasopharyngeal viral concentration on presentation was measured by real-time PCR to evaluate shedding from the upper respiratory tract. Serial upper and lower respiratory tract specimens were monitored to determine preferential tropism and document virological response to treatment. Results The frequency of D222G infection was 17.4% among cases with severe pneumonia, and 26.7% among cases requiring intensive care. Altogether, four sporadic D222G cases spread across the first and second waves in Hong Kong were detected. A significant association between D222G infection with severe pneumonia (100% vs. 32.2%, P = 0.015) and intensive care admission (100% vs. 18.6%, P = 0.002) was observed. D222G was associated with lower concentrations of virus in the upper respiratory tract compared to wildtype, but persisted in the lower respiratory tract at high concentrations, despite clearance from the upper respiratory tract following antiviral treatment. Conclusions These observations suggest that D222G can arise de novo , sheds less virus from the upper respiratory tract and may be less transmissible, but more pneumotropic and more resistant to antiviral treatment. D222G is associated with a higher chance of developing critical disease. Lower respiratory tract specimen is needed for a reliable detection of this mutant.

Background Fever is an undifferentiated clinical feature that may enhance the sensitivity of syndromic surveillance systems. By studying the spatiotemporal associations of febrile patients, it may allow early detection of case clustering that indicates imminent threat of infectious disease outbreaks in the community. Methods We captured consecutive emergency department visits that led to hospitalization in a district hospital in Hong Kong during the period of 12 Sep 2005 to 14 Oct 2005. We recorded demographic data, provisional diagnoses, temperature on presentation and residential location for each patient-episode, and geocoded the residential addresses. We applied Geographical Information System technology to study the geographical distribution these cases, and their associations within a 50-m buffer zone spatially. A case cluster was defined by three or more spatially associated febrile patients within each three consecutive days. Results One thousand and sixty six patient-episodes were eligible for analysis; 42% of them had fever (>37°C; oral temperature) on presentation. Two hundred and four patient-episodes (19.1%) came from residential care homes for elderly (RCHE). We detected a total of 40 case clusters during the study period. Clustered cases were of older age; 57 (33.3%) were residents of RCHE. We found a median of 3 patients (range: 3 - 8) and time span of 3 days (range: 2 - 8 days) in each cluster. Twenty five clusters had 2 or more patients living in the same building block; 18 of them were from RCHE. Conclusions It is technically feasible to perform surveillance on febrile patients and studying their spatiotemporal associations. The information is potentially useful for early detection of impending infectious disease threats.

We retrospectively analyzed 92 cases of severe rickettsial infections in patients (median age = 49 years, 57% male, 37.0% with scrub typhus) in Hong Kong. Immunofluorescence assay was used for diagnostic confirmation. Identification ofor = 1 diagnostic sign (exposure history, rash, or eschar) was possible in 94.6% of the cases. Multivariate analysis suggested that pulmonary infiltrates (odds ratio [OR] = 25.2, 95% confidence interval [CI] = 3.9-160.9, P = 0.001) and leukocytosis (OR = 1.3, 95% CI = 1.0-1.5 per unit increase, P = 0.033) were independent predictors of admission to an intensive care unit (14.1%). Delayed administration of doxycycline was independently associated with major organ dysfunction (23.9%; oxygen desaturation, renal failure, severe jaundice, encephalopathy, cardiac failure) (OR = 1.2, 95% CI = 1.0-1.5 per day delay, P = 0.046; adjusted for age and rickettsia biogroup) and prolonged hospitalization10 days (25%) (OR = 1.4, 95% CI = 1.1-1.9 per day delay, P = 0.014). Treatment with fluoroquinolone/clarithromycin did not correlate with clinical outcomes (P0.05). Early empirical doxycycline therapy should be considered if clinico-epidemiologic signs of rickettsial infections are present.

Understanding factors affecting length of hospital stay (LOS) in patients with severe influenza may improve their management.A retrospective cohort study on laboratory-confirmed, adult influenza patients hospitalized in 2004 and 2005 was conducted. For all influenza cases during that period, immunofluorescence assay on nasopharyngeal aspirate was used for rapid diagnosis, and oseltamivir (75 mg twice daily for 5 days) prescribed if the patient presented within 2 days of symptom onset. Independent factors associated with time to discharge were identified using Cox proportional hazards models. An adjusted hazard ratio (aHR)1 signifies a higher chance of early discharge. Viral shedding and influenza vaccination history were studied during one 'flu' season.A total of 356 patients (influenza A 93.5%) were studied. The majority of patients were old (70.2 +/- 8.4 years), hador = 1 comorbid illness (69.1%) and developed respiratory or cardiovascular complications (69.4%). Oseltamivir initiated within 2 days of illness was associated with shorter total LOS (Kaplan-Meier estimated median 4 versus 6 days [-33%]; aHR for discharge 1.54, 95% confidence intervals [95% CI] 1.23-1.92, P0.0001). Older age (or = 70 years), comorbidities and complications were associated with prolonged LOS. Prolonged viral RNA detectionday 4 of illness (23 out of 99 consecutive patients) was also independently associated with longer LOS (aHR 0.36 [95% CI 0.19-0.71], P = 0.003), whereas influenza vaccination within 6 months was associated with shorter LOS (aHR 2.14 [95% CI 1.18-3.85], P = 0.012).Our analyses suggest that timely oseltamivir treatment is independently associated with shorter LOS in patients hospitalized for severe influenza. Efforts to ensure early diagnosis and therapeutic intervention are warranted.

Background It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients. Method One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. Results There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care. Conclusion The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection.

Severe acute respiratory syndrome (SARS) has become a global public health emergency.To evaluate the characteristics and outcomes of patients with SARS in Hong Kong and to identify predictors of mortality.Retrospective cohort study.Quarantine hospital for patients with SARS in Hong Kong.267 consecutive patients hospitalized from 26 February to 31 March 2003 for probable or confirmed SARS.Clinical, laboratory, and radiographic measures; 3-month mortality rate.According to our case definition, there were 227 cases of confirmed SARS and 40 cases of probable SARS. Common presenting symptoms were fever (99% of patients), chills (74%), malaise (63%), and myalgia (50%). Laboratory findings included lymphopenia (73%), thrombocytopenia (50%), hyponatremia (60%), and elevated levels of lactate dehydrogenase (47%) and C-reactive protein (75%). During hospitalization, incidence of diarrhea (53%), anemia (53%), and acute renal failure (6%) increased. Sixty-nine patients (26%) required intensive care because of respiratory failure. The 3-month mortality rate was 12% (95% CI, 8% to 16%). Factors contributing to mortality were respiratory failure, acute renal failure, and nosocomial sepsis. On multivariate Cox regression, age older than 60 years (relative risk, 5.10 [CI, 2.30 to 11.31]; P0.001) and lactate dehydrogenase level greater than 3.8 micro kat/L at presentation (relative risk, 2.20 [CI, 1.03 to 4.71]; P = 0.04) were independent predictors of mortality.Because of the longer follow-up period in our cohort, the mortality rate in these patients is higher than rates reported in previous studies. Advanced age and high lactate dehydrogenase level at presentation predict mortality. *For members of the Princess Margaret Hospital SARS Study Group, see the Appendix.