Jasper Fw Chan

Prevention of nosocomial transmission of swine-origin pandemic influenza virus A/H1N1 by infection control bundle

n Summaryn n After the outbreak of severe acute respiratory syndrome in Hong Kong, the importance of preventing nosocomial transmission of respiratory viruses has become a top priority in infection control. During the containment and early mitigation phases of the swine-origin influenza virus (S-OIV) A H1N1 pandemic, an infection control bundle consisting of multiple coherent measures was organised by our infection control team to minimise nosocomial transmission. This included repeated open staff forum achieving high attendance; early recognition of index cases among inpatients by liberal testing; early relief of sick staff from work; directly observed hand hygiene practice during outbreaks; and monitoring of compliance with infection control practice. During the first 100 days (from 1 May to 8 August 2009) when the first 100 laboratory-confirmed patients with S-OIV and 12 infected healthcare workers (HCWs) were identified, a total of 836 asymptomatic exposed persons (184 patients and 652 HCWs) were required to undergo a seven-day medical surveillance. The infection control nurses monitored them for the onset of symptoms. Four (0.48%) exposed persons (one house officer, two non-clinical staff, and one patient) were virologically confirmed with S-OIV. Not wearing a surgical mask either by the exposed persons during contact with the index cases (4/4 vs 264/832, Pn =0.010) or vice versa (4/4 vs 300/832, Pn =0.017, Fishers exact test) were found to be significant risk factors for nosocomial acquisition of S-OIV.n n

Sequential introduction of single room isolation and hand hygiene campaign in the control of methicillin-resistant Staphylococcus aureus in intensive care unit

BackgroundAfter renovation of the adult intensive care unit (ICU) with installation of ten single rooms, an enhanced infection control program was conducted to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) in our hospital.MethodsSince the ICU renovation, all patients colonized or infected with MRSA were nursed in single rooms with contact precautions. The incidence of MRSA infection in the ICU was monitored during 3 different phases: the baseline period (phase 1); after ICU renovation (phase 2) and after implementation of a hand hygiene campaign with alcohol-based hand rub (phase 3). Patients infected with extended spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella species were chosen as controls because they were managed in open cubicles with standard precautions.ResultsWithout a major change in bed occupancy rate, nursing workforce, or the protocol of environmental cleansing throughout the study period, a stepwise reduction in ICU onset nonbacteraemic MRSA infection was observed: from 3.54 (phase 1) to 2.26 (phase 2, p = 0.042) and 1.02 (phase 3, p = 0.006) per 1000-patient-days. ICU onset bacteraemic MRSA infection was significantly reduced from 1.94 (phase 1) to 0.9 (phase 2, p = 0.005) and 0.28 (phase 3, p = 0.021) per 1000-patient-days. Infection due to ESBL-producing organisms did not show a corresponding reduction. The usage density of broad-spectrum antibiotics and fluoroquinolones increased from phase 1 to 3. However a significant trend improvement of ICU onset MRSA infection by segmented regression analysis can only be demonstrated when comparison was made before and after the severe acute respiratory syndrome (SARS) epidemic. This suggests that the deaths of fellow healthcare workers from an occupational acquired infection had an overwhelming effect on their compliance with infection control measures.ConclusionProvision of single room isolation facilities and promotion of hand hygiene practice are important. However compliance with infection control measures relies largely on a personal commitment, which may increase when personal safety is threatened.

Talaromyces (Penicillium) marneffei infection in non-HIV-infected patients

Talaromyces (Penicillium) marneffei is an important pathogenic thermally dimorphic fungus causing systemic mycosis in Southeast Asia. The clinical significance of T. marneffei became evident when the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome epidemic arrived in Southeast Asia in 1988. Subsequently, a decline in the incidence of T. marneffei infection among HIV-infected patients was seen in regions with access to highly active antiretroviral therapy and other control measures for HIV. Since the 1990s, an increasing number of T. marneffei infections have been reported among non-HIV-infected patients with impaired cell-mediated immunity. Their comorbidities included primary adult-onset immunodeficiency due to anti-interferon-gamma autoantibodies and secondary immunosuppressive conditions including other autoimmune diseases, solid organ and hematopoietic stem cell transplantations, T-lymphocyte-depleting immunsuppressive drugs and novel anti-cancer targeted therapies such as anti-CD20 monoclonal antibodies and kinase inhibitors. Moreover, improved immunological diagnostics identified more primary immunodeficiency syndromes associated with T. marneffei infection in children. The higher case-fatality rate of T. marneffei infection in non-HIV-infected than HIV-infected patients might be related to delayed diagnosis due to the lack of clinical suspicion. Correction of the underlying immune defects and early use of antifungals are important treatment strategies. Clinicians should be familiar with the changing epidemiology and clinical management of T. marneffei infection among non-HIV-infected patients.

Transmission of methicillin-resistant staphylococcus aureus in the long term care facilities in Hong Kong

BackgroundThe relative contribution of long term care facilities (LTCFs) and hospitals in the transmission of methicillin-resistant Staphylococcus aureus (MRSA) is unknown.MethodsConcurrent MRSA screening and spa type analysis was performed in LTCFs and their network hospitals to estimate the rate of MRSA acquisition among residents during their stay in LTCFs and hospitals, by colonization pressure and MRSA transmission calculations.ResultsIn 40 LTCFs, 436 (21.6%) of 2020 residents were identified as ‘MRSA-positive’. The incidence of MRSA transmission per 1000-colonization-days among the residents during their stay in LTCFs and hospitals were 309 and 113 respectively, while the colonization pressure in LTCFs and hospitals were 210 and 185 per 1000-patient-days respectively. MRSA spa type t1081 was the most commonly isolated linage in both LTCF residents (76/121, 62.8%) and hospitalized patients (51/87, 58.6%), while type t4677 was significantly associated with LTCF residents (24/121, 19.8%) compared with hospitalized patients (3/87, 3.4%) (pu2009<u20090.001). This suggested continuous transmission of MRSA t4677 among LTCF residents. Also, an inverse linear relationship between MRSA prevalence in LTCFs and the average living area per LTCF resident was observed (Pearson correlation −0.443, pu2009=u20090.004), with the odds of patients acquiring MRSA reduced by a factor of 0.90 for each 10 square feet increase in living area.ConclusionsOur data suggest that MRSA transmission was more serious in LTCFs than in hospitals. Infection control should be focused on LTCFs in order to reduce the burden of MRSA carriers in healthcare settings.

Immunogenicity of Intradermal Trivalent Influenza Vaccine With Topical Imiquimod: A Double Blind Randomized Controlled Trial

BACKGROUNDnImiquimod, a synthetic Toll-like receptor 7 agonist enhanced immunogenicity of influenza vaccine in a mouse model. We hypothesized that topical imiquimod before intradermal influenza vaccination (TIV) would produce similar effect in human.nnnMETHODSnWe performed a prospective 1-year follow-up, double-blind, randomized, controlled trial with adults with comorbidities. Participants were randomized to 1 of the following 3 vaccinations: topical 5% 250 mg imiquimod ointment followed by intradermal TIV, topical aqueous-cream followed by intradermal TIV, or topical aqueous-cream followed by intramuscular TIV. Patients and investigators were blinded to the type of topical treatment applied. Hemagglutination inhibition (HI) and microneutralization antibody titers were measured. The primary outcome was the day 7 seroconversion rate.nnnRESULTSnNinety-one recruited participants completed the study. The median age was 73 years. On day 7, 27/30 (90%) patients who received imiquimod and intradermal TIV achieved seroconversion against the H1N1 strain by HI, compared with 4/30 (13.3%) who received aqueous-cream and intramuscular TIV (P < .001), and 12/31 (38.7%) who received aqueous-cream and intradermal TIV (P < .001). The seroconversion, seroprotection, and geometric mean titer-fold increase were met in all 3 strains in the imiquimod and intradermal TIV group 2 weeks earlier, and the better seroconversion rate was sustained from day 7 to year 1 (P ≤ .001). The better immunogenicity was associated with fewer hospitalizations for influenza or pneumonia (P < .05). All adverse reactions were self-limited.nnnCONCLUSIONSnPretreatment with topical imiquimod significantly expedited, augmented, and prolonged the immunogenicity of influenza vaccination. This strategy for influenza immunization should be considered for the elderly population.

Decolonization of gastrointestinal carriage of vancomycin-resistant Enterococcus faecium: case series and review of literature

BackgroundProlonged asymptomatic carriage of vancomycin-resistant enterococci (VRE) in the gastrointestinal tract and the lack of effective decolonization regimen perpetuate the endemicity of VRE in the healthcare settings.Case presentationWe report a regimen for decolonization of gastrointestinal carriage of VRE by a combination of environmental disinfection, patient isolation, bowel preparation to wash-out the fecal bacterial population using polyethylene glycol, a five-day course of oral absorbable linezolid and non-absorbable daptomycin to suppress any remaining VRE, and subsequent oral Lactobacillus rhamnosus GG to maintain the colonization resistance in four patients, including two patients with end-stage liver cirrhosis, one patient with complication post liver transplant, and one patient with complicated infective endocarditis. All patients had clearance of VRE immediately after decolonization, and 3 of them remained VRE-free for 23 to 137 days of hospitalization, despite subsequent use of intravenous broad-spectrum antibiotics without anti-VRE activity.ConclusionThis strategy should be further studied in settings of low VRE endemicity with limited isolation facilities.

A sensitive and specific antigen detection assay for Middle East respiratory syndrome coronavirus

Since its emergence in 2012, more than 900 laboratory-confirmed cases of Middle East respiratory syndrome (MERS) have been reported with a fatality rate of more than 30%. However, no antigen detection assay for commercial use is available for diagnosis. In this study, the full-length nucleocapsid protein (NP) gene of MERS coronavirus (MERS-CoV) was cloned and expressed in Escherichia coli. A MERS-CoV NP capture enzyme-linked immunosorbent assay (ELISA) using two MERS-CoV-NP-specific monoclonal antibodies (MAbs) generated was developed. The ELISA was evaluated using 129 nasopharyngeal aspirates (NPAs) positive for various respiratory viruses and simulated positive NPAs by adding serial dilutions of MERS-CoV. Using a cutoff OD of 0.19, all 129 NPAs positive for respiratory viruses showed very low OD, with a specificity of 100%. For the two simulated MERS-CoV-positive NPAs with serial dilutions of live MERS-CoV, all samples with ≥10 50% tissue culture infective dose (TCID50)/0.1 mL showed positive results. For the 10xa0additional NPAs with 20 and 200 TCID50/0.1 mL of live MERS-CoV added, all were positive. A highly sensitive and specific MAbs-based antigen capture ELISA has been developed for MERS. This sensitive and specific antigen capture ELISA should be useful for detection of MERS-CoV in human and dromedaries and in field studies.Emerging Microbes & Infections (2015) 4, e26; doi:10.1038/emi.2015.26; published online 22 April 2015

Identification of specific metabolites in culture supernatant of Mycobacterium tuberculosis using metabolomics: exploration of potential biomarkers

Although previous studies have reported the use of metabolomics for Mycobacterium species differentiation, little is known about the potential of extracellular metabolites of Mycobacterium tuberculosis (MTB) as specific biomarkers. Using an optimized ultrahigh performance liquid chromatography–electrospray ionization–quadruple time of flight–mass spectrometry (UHPLC–ESI–Q–TOF–MS) platform, we characterized the extracellular metabolomes of culture supernatant of nine MTB strains and nine non-tuberculous Mycobacterium (NTM) strains (four M. avium complex, one M. bovis Bacillus Calmette–Guérin (BCG), one M. chelonae, one M. fortuitum and two M. kansasii). Principal component analysis readily distinguished the metabolomes between MTB and NTM. Using multivariate and univariate analysis, 24 metabolites with significantly higher levels in MTB were identified. While seven metabolites were identified by tandem mass spectrometry (MS/MS), the other 17 metabolites were unidentified by MS/MS against database matching, suggesting that they may be potentially novel compounds. One metabolite was identified as dexpanthenol, the alcohol analog of pantothenic acid (vitamin B5), which was not known to be produced by bacteria previously. Four metabolites were identified as 1-tuberculosinyladenosine (1-TbAd), a product of the virulence-associated enzyme Rv3378c, and three previously undescribed derivatives of 1-TbAd. Two derivatives differ from 1-TbAd by the ribose group of the nucleoside while the other likely differs by the base. The remaining two metabolites were identified as a tetrapeptide, Val-His-Glu-His, and a monoacylglycerophosphoglycerol, phosphatidylglycerol (PG) (16∶0/0∶0), respectively. Further studies on the chemical structure and biosynthetic pathway of these MTB-specific metabolites would help understand their biological functions. Studies on clinical samples from tuberculosis patients are required to explore for their potential role as diagnostic biomarkers.

Successful control of vancomycin-resistant Enterococcus faecium outbreak in a neurosurgical unit at non-endemic region

Vancomycin-resistant enterococci (VRE) have emerged in many parts of the world, but have only been reported sporadically in Hong Kong. We report an outbreak of vancomycin-resistant Enterococcus faecium (VREfm) in a neurosurgical unit at a tertiary teaching hospital between 3 March and 3 April 2009 in Hong Kong. During the outbreak investigation, clinical samples from 193 (91.5%) of 211 patients who had stayed in the neurosurgical unit and 506 environmental samples were screened for VREfm. Besides the index case, another 3 (1.6%) out of 192 patients were found to be positive for VREfm. Two (0.4%) out of 506 environmental samples were positive for VREfm. All four clinical and two environmental isolates were found to be clonally related by pulse-field gel electrophoresis. The risk factors for nosocomial acquisition of VREfm included advanced age (P=0.047), presence of nasogastric tubing (P=0.002) and tracheostomy (P<0.001), and the use of β-lactam antibiotics (P<0.001) and vancomycin (P=0.001). Contrary to other VRE outbreaks in which the spread was rapid, the neurosurgical patients’ immobilization because of coma and mechanical ventilation dependency, and the vigilant practice of hand hygiene by health-care workers successfully limited the number of secondary cases despite the delayed recognition of the index case. All patients with VREfm were labeled in the hospital network information system so that stringent infection control measures with contact precautions would be carried out once these patients were readmitted to prevent its spread in our locality.

Clinical characteristics and molecular epidemiology of hepatitis E in Shenzhen, China: a shift toward foodborne transmission of hepatitis E virus infection

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in China. Recently, a shift in molecular epidemiology from hepatitis E genotype 1 (HEV-1) to hepatitis E genotype 4 (HEV-4) has been observed in Northern China, marking a switch from human-to-human transmission to zoonosis. However, similar data from cities in Southern China are lacking. This observational study of human hepatitis E cases in Shenzhen, a metropolitan city in the Pearl River Delta region, aimed to describe the clinical features and molecular epidemiology of hepatitis E in Southern China. Over a 55-month period, we identified 20 patients with acute hepatitis E. Most were middle-aged men, and 50% of patients had concomitant liver disease, of whom 70% were identified to have non-alcoholic fatty liver disease; such patients had a trend toward higher liver enzymes. Quantitative real-time RT-PCR using archived serum samples showed that 12 patients had hepatitis E viremia at presentation. Sequencing of the RNA-dependent RNA polymerase gene was performed for five of these patients, and phylogenetic analysis revealed that these five HEV isolates belonged to subgenotype 4b and were clustered with swine HEV isolates from Southern China. Combined with other studies showing similar findings, this suggests that the molecular epidemiology of hepatitis E in China is evolving toward low-level endemicity driven by foodborne transmission from seafood or pork products. The importance of concomitant liver disease, in particular non-alcoholic fatty liver disease, as a risk factor for severe hepatitis E requires further study. Emerging Microbes & Infections (2017) 6, e115 doi:10.1038/emi.2017.107; published online 20 December 2017