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Objectives : We aim to study the viral kinetics and host inflammatory response of RSV infection in older adults, and their correlation with disease severity. Methods : We performed a prospective observational study in adults with RSV infection. We serially collected nasal-throat swabs for quantification of RSV-A and RSV-B viral load, and peripheral blood samples for measurement of cytokine/chemokine concentrations. The study endpoints were (i) requiring supplemental oxygen therapy, and (ii) non-invasive ventilation, intensive care, or died within 30 days of admission. We performed multivariable logistic regression models to identify independent variables for severe disease. Results : We enrolled 71 hospitalized patients and 10 outpatients treated for RSV infection (median age 75 years, 51% male, and 74% with comorbidities). Among hospitalized patients, 61% required supplemental oxygen therapy, and 18% had severe disease requiring non-invasive ventilation or intensive care, or died within 30 days. Inflammatory cytokine/chemokines IL-6, CXCL8/IL-8, CXCL9/MIG and CXCL10/IP-10 increased significantly during the acute phase of illness. IL-6 concentration was independently associated with severe disease after adjusting for confounding factors. RSV viral load was not associated with disease severity throughout the course of illness. Conclusion : Host inflammatory response is a major marker of severe disease in older adults with RSV infection.

The annual epidemics of seasonal influenza is partly attributed to the continued virus evolution. It is challenging to evaluate the effect of influenza virus mutations on evading population immunity. In this study, we introduce a novel statistical and computational approach to measure the dynamic molecular determinants underlying epidemics using effective mutations (EMs), and account for the time of waning mutation advantage against herd immunity by measuring the effective mutation periods (EMPs). Extensive analysis is performed on the sequencing and epidemiology data of H3N2 epidemics in ten regions from season to season. We systematically identified 46 EMs in the hemagglutinin (HA) gene, in which the majority were antigenic sites. Eight EMs were located in immunosubdominant stalk domain, an important target for developing broadly reactive antibodies. The EMs might provide timely information on key substitutions for influenza vaccines antigen design. The EMP suggested that major genetic variants of H3N2 circulated in South-east Asia for an average duration of 4.5 years (SD 2.4) compared to a significantly shorter 2.0 years (SD 1.0) in temperate regions. The proposed method bridges population epidemics and molecular characteristics of infectious diseases, and would find broad applications in various pathogens mutation estimations.

The effectiveness of seasonal influenza vaccines varies with the matching of vaccine strains to circulating strains. Based on the genetic distance of hemagglutinin and neuraminidase gene of the influenza viruses to vaccine strains, we statistically quantified the relationship between the genetic mismatch and vaccine effectiveness (VE) for influenza A/H1N1pdm09, A/H3N2 and B. We also proposed a systematic approach to integrate multiple genes and influenza types for overall VE estimation. Evident linear relationships were identified and validated in independent data. The modelling framework may enable in silico prediction for VE on a real-time basis and inform the influenza vaccine selection strategy.

Background Rotavirus is a common infectious cause of childhood hospitalisation in Hong Kong. Rotavirus vaccines have been used in the private sector since licensure in 2006 but have not been incorporated in the government’s universal Childhood Immunisation Programme. This study aimed to evaluate rotavirus vaccine effectiveness against hospitalisation. Methods This case-control study was conducted in the 2014/2015 rotavirus season in six public hospitals. Hospitalised acute gastroenteritis patients meeting inclusion criteria were recruited and copies of their immunisation records were collected. Case-patients were defined as enrolled subjects with stool specimens obtained in the first 48 h of hospitalisation that tested positive for rotavirus, whereas control-patients were those with stool specimens obtained in the first 48 h of hospitalisation testing negative for rotavirus. Vaccine effectiveness for administration of at least one dose of either Rotarix ® (GlaxoSmithKline Biologicals) or RotaTeq ® (Merck Research Laboratories) was calculated as 1 minus the odds ratio for rotavirus vaccination history for case-patients versus control-patients. Results Among the 525 eligible subjects recruited, immunisation records were seen in 404 (77%) subjects. 31% (162/525 and 126/404) tested positive for rotavirus. In the 404 subjects assessed for vaccine effectiveness, 2.4% and 24% received at least 1 dose of either rotavirus vaccine in case- and control-patients respectively. The unmatched vaccine effectiveness against hospitalisation for administration of at least one dose of either rotavirus vaccines was 92% (95% confidence interval [CI]: 75%, 98%). The matched analyses by age only and both age and admission date showed 96% (95% CI: 72%, 100%) and 89% (95% CI: 51%, 97%) protection against rotavirus hospitalisation respectively. Conclusions Rotavirus vaccine is highly effective in preventing hospitalisation from rotavirus disease in young Hong Kong children.

Background Cyclovirus (CyCV) Malawi strain VS5700009 has recently been discovered and reported in clinical cerebrospinal fluid (CSF) samples. Further epidemiological and case-control studies are warranted. The availability of a highly sensitive and specific detection assay for this new virus is thus crucial. Objectives To evaluate the performance of the first and the only available PCR assay for CyCV-VS5700009. Study design A total of 100 CSF samples collected during January–December 2010 were selected for PCR detection of CyCV-VS5700009. Positive PCR amplicons were subjected to sequencing confirmation and BLAST analysis. Results Initial PCR screening for CyCV-VS5700009 identified one sample, showing a PCR band of expected size (380 bp). Sequencing and BLAST analysis, however, indicated that the band was 364 bp in length and showed >99% nucleotide homology to a human gene known as nuclear receptor coactivator 6 (NCOA6). Pairwise sequence alignment confirmed that both the forward and reverse PCR primers used had significant homology (>70%) to NCOA6. None of the CSF samples tested were positive for CyCV-VS5700009. Conclusions The original PCR assay for CyCV-VS5700009 detection may have potential cross-reactivity with contaminating human genomic DNA. The assay may be of little diagnostic use on clinical specimens that are rich in host DNA such as biopsy tissues.

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.

We characterized the effects of selective Cox-2 inhibition on the angiogenesis gastric cancer cell line SGC7901 by stable transfection of antisense Cox-2 cDNA (Cox-2-AS) or pharmacological inhibition by selective cox-2 inhibitor (NS398). The conditioned media obtained from SGC7901 treated with Cox-2-AS or NS398 suppressed the proliferation, migration and tube formation of human umbilical vein endothelial cells. Moreover, both treatments inhibited in vivo angiogenesis. These inhibitions could be partially reversed by the addition of PGE2. Our findings support that selective inhibition of Cox-2 alone plays an instrumental role on gastric cancer associated angiogenesis.

Background Influenza virus infections are causing substantial morbidity and mortality, despite availability of antiviral treatments. Macrolides have been shown to ameliorate inflammation in respiratory diseases and provide clinical benefits. Data in influenza, however, are scarce. We aimed to assess the anti-inflammatory effects of macrolide treatment in patients with influenza, and its effects on viral clearance and symptom resolution. Methods In this open-label, multicentre, randomised controlled trial, we recruited adults admitted to hospital for laboratory-confirmed influenza in Hong Kong. Key inclusion criteria were age 18 years or older, influenza A and B virus infections confirmed by PCR or immunofluorescence assays, and presentation within 4 days from illness onset. Patients were randomly assigned (1:1) using a computer-generated sequence to oseltamivir (75 mg twice daily) plus azithromycin (500 mg per day) or oseltamivir (75mg twice daily) alone, both given orally for 5 days. The primary outcome was change in plasma cytokine and chemokine concentration over time (day 0–10), analysed by intention to treat. Generalised estimating equation (GEE) models were used to analyse longitudinal data, and were adjusted for potential confounders. Ethics approvals were obtained from the institutional review bodies of all participating institutes. All patients provided written informed consent. This trial is registered with ClinicalTrials.gov, number NCT01779570. Findings During the influenza seasons beginning from 2013–14 through to 2015–16, 50 patients were randomly assigned to the oseltamivir-azithromycin (n=25) or oseltamivir (n=25) groups, with similar baseline characteristics (mean age 54·7 years [SD 18·5] in the oseltamivir-azithromycin group vs 58·6 years [18·1] in the oseltamivir group; 16 [64%] of 25 patients in the oseltamivir-azithromycin group were men vs 15 [60%] of 25 in the oseltamivir group). Three key pro-inflammatory cytokines declined faster in the oseltamivir-azithromycin group than in the oseltamivir group: interleukin (IL)-6 (GEE β=–0·037 [95% CI −0·067 to −0·007], p=0·016; change from baseline −83·4% vs −59·5%), IL-17 (β=–0·064 [–0·117 to −0·012], p=0·015; −74·0% vs −34·3%), and CXCL9 (β=–0·010 [–0·020 to 0·000], p=0·043; −71·3% vs −56·0%). Non-significant differences in the following cytokines were observed between treatment groups: CXCL8 (β=–0·018 [–0·037 to 0·000], p=0·056; −80·5% vs −58·0%), sTNFR-1 (β=–0·003 [–0·006 to 0·000], p=0·084; −40·1% vs −24·8%), IL-18 (β=–0·006 [–0·015 to 0·003], p=0·197; −29·1% vs 30·2%), and C-reactive protein (β=–0·033 [–0·088 to 0·022], p>0·10; −77·5% vs −48·2%). Two serious adverse events (SAEs) occurred in the oseltamivir-azithromycin group (Pseudomonas aeruginosa pneumonia, post-influenza vestibular neuronitis onset after stopping treatment for 1 week) versus one SAE in the oseltamivir group (increased ascites; p>0·99); all SAEs were considered unrelated to treatment. Other common adverse events were gastrointestinal or hepatic symptoms (five [20%] of 25 in the oseltamivir-azithromycin group vs four [16%] of 25 in the oseltamivir group; p>0.99) and dizziness or hearing symptoms (two [8%] vs two [8%]; p>0·99). All events were transient and reversible, and no participants died in this study. Interpretation We found significant anti-inflammatory effects with adjunctive macrolide treatment in adults with severe influenza infection. The clinical benefits of a macrolide-containing regimen deserve further study. Funding Research Grant Council of the Government of the Hong Kong Special Administrative Region, China (468112).

Background Whether host genetic factors determine clinical severity of influenza virus infections is unclear. This study examined the effects of single nucleotide polymorphisms (SNPs) of IFITM3, TLR3, CD55 , and TLR4 genes on outcomes of avian influenza A (H7N9) and pandemic influenza A (H1N1) pdm09 in Chinese patients. Methods This multicentre cohort study took place in four centres in Hong Kong, Beijing, Guangdong, and Shanghai and included adults prospectively diagnosed with H7N9 and H1N1 pdm09 infections during three respective seasonal outbreaks (H7N9, 2013–15; H1N1 pdm09 , 2011–14). The inclusion criteria were PCR-confirmed H7N9 or H1N1 pdm09 virus infection, age 18 years or older, and Chinese ethnicity. Host DNA was extracted from diagnostic respiratory samples, and IFITM3 (rs12252), TLR3 (rs5743313), CD55 (rs2564978), and TLR4 (rs4986790/4986791) were genotyped by Sanger sequencing. The data were tested to see whether they deviated from the Hardy-Weinberg equilibrium, and were compared with the 1000 Genomes data. The primary outcome for analysis was mortality. The effects of the SNPs were examined under different genetic models (recessive, additive, and dominant). The joint effect of significant loci was tested by computing the genetic risk score. All identifying patient information was removed from the dataset, and only anonymous data were used for analysis; individual consent was not required. Ethics approvals were obtained from the institutional review boards of all participating institutes. Findings Our cohort consisted of 275 adults with H7N9 and H1N1 pdm09 infections, of whom 33 died. In patients who died, we found over-representation of the homozygous IFITM3 CC genotype (18 [54%] of 33 patients with available data who died vs 70 [33%] of 211 with available data who survived; p=0·017) and the TLR3 CC genotype (28 [93%] of 30 vs 160 [77%] of 208; p=0·039). Recessive genetic models, adjusted for age, comorbidity, and antiviral treatment, showed that these genotypes had a significant association with increased risk of death ( IFITM3 CC genotype, adjusted hazard ratio [HR] 2·78 [95% CI 1·29–6·02]; and TLR3 CC genotype, adjusted HR 4·85 [1·11–21·06]). Cumulative effects were found (adjusted HR 3·53 [95% CI 1·64–7·59] per risk genotype; adjusted HR 9·99 [1·27–78·59] with both genotypes). The case-fatality rate in patients with a genetic risk score of 2, 1, and 0 was 23%, 11%, and 3%, respectively. Results were similar for each influenza subtype and other severity indicators such as development of acute respiratory failure. The population-attributable risk for mortality was 35·5% (95% CI 9·9–69·8) for IFITM3 CC and 74·6% (21·7–100) for TLR3 CC (combined effect, 83·6% [52·3–100]), owing to their high prevalence among Chinese people. A SNP of CD55 (genotype TT) was linked to severity of influenza as indicated by an increased risk for hospital admission (adjusted odds ratio [OR] 2·77, 95% CI 1·21–6·36; p=0·02); TLR4 was shown to be non-polymorphic in this cohort. Interpretation Host genetic factors might influence clinical outcomes of avian and pandemic influenza. Our findings could have important implications on public health and health-care planning, patient care, and design of clinical trials. Funding Health and Medical Research Fund (RRG-09) of the Hong Kong Special Administrative Region, China.

A 75-year-old woman presented with influenza-like sympoms which included fever, cough, and shortness of breath was dmitted to our hospital in September 2006 (defined as hospital ay 1). She had underlying hypertension, ischemic heart disase, atrial fibrillation, congestive heart failure, and renal artery tenosis. On admission, she was diagnosed to have chest infecion and exacerbation of heart failure symptoms. Oxygen therapy, iuretics and co-amoxiclav were given. Seasonal influenza A H3N2) virus infection was confirmed by virus subtype-specific everse-transcriptase-polymerase-chain-reaction (RT-PCR) assay f a nasopharyngeal aspirate collected at presentation. No antivial treatment was given because of late presentation beyond 48h fter symptom onset. She developed diarrhea since day 3 and

Psychrobacter species rarely cause infections in human. We reported herein a 62-year-old cirrhotic patient who presented with fever and diarrhoea after the consumption of raw geoduck clam. Blood culture grew Psychrobacter phenylpyruvicus which was sensitive to most anti-microbial agents. The patient responded promptly to intravenous antibiotics. This is the first report of human infection with this unusual organism which illustrates the potential health hazards of eating raw geoduck clam in patients with advanced liver disease.