Temporal and Gene Reassortment Analysis of Influenza C Virus Outbreaks in Hong Kong, SAR, China.

From 2014 to week 07/2020 the Centre for Health Protection in Hong Kong conducted screening for influenza C virus (ICV). A retrospective analysis of ICV detections to week 26/2019 revealed persistent low-level circulation with outbreaks occurring biennially in the winters of 2015 to 2016 and 2017 to 2018 (R. S. Daniels et al., J Virol 94:e01051-20, 2020, https://doi.org/10.1128/JVI.01051-20). Here, we report on an outbreak occurring in 2019 to 2020, reinforcing the observation of biennial seasonality in Hong Kong. All three outbreaks occurred in similar time frames, were subsequently dwarfed by seasonal epidemics of influenza types A and B, and were caused by similar proportions of C/Kanagawa/1/76 (K)-lineage and C/São Paulo/378/82 S1- and S2-sublineage viruses. Ongoing genetic drift was observed in all genes, with some evidence of amino acid substitution in the hemagglutinin-esterase-fusion (HEF) glycoprotein possibly associated with antigenic drift. A total of 61 ICV genomes covering the three outbreaks were analyzed for reassortment, and 9 different reassortant constellations were identified, 1 K-lineage, 4 S1-sublineage, and 4 S2-sublineage, with 6 of these being identified first in the 2019-1920 outbreak (2 S2-lineage and 4 S1-lineage). The roles that virus interference/enhancement, ICV persistent infection, genome evolution, and reassortment might play in the observed seasonality of ICV in Hong Kong are discussed. IMPORTANCE Influenza C virus (ICV) infection of humans is common, with the great majority of people being infected during childhood, though reinfection can occur throughout life. While infection normally results in "cold-like" symptoms, severe disease cases have been reported in recent years. However, knowledge of ICV is limited due to poor systematic surveillance and an inability to propagate the virus in large amounts in the laboratory. Following recent systematic surveillance in Hong Kong SAR, China, and direct ICV gene sequencing from clinical specimens, a 2-year cycle of disease outbreaks (epidemics) has been identified, with gene mixing playing a significant role in ICV evolution. Studies like those reported here are key to developing an understanding of the impact of influenza C virus infection in humans, notably where comorbidities exist and severe respiratory disease can develop.

Molecular Characterization of Influenza C Viruses from Outbreaks in Hong Kong SAR, China.

In 2014, the Centre for Health Protection in Hong Kong introduced screening for influenza C virus (ICV) as part of its routine surveillance for infectious agents in specimens collected from patients presenting with symptoms of respiratory viral infection, including influenza-like illness (ILI). A retrospective analysis of ICV detections up to week 26 of 2019 revealed persistent low-level circulation, with two outbreaks having occurred in the winters of 2015 to 2016 and 2017 to 2018. These outbreaks occurred at the same time as, and were dwarfed by, seasonal epidemics of influenza types A and B. Gene sequencing studies on stored ICV-positive clinical specimens from the two outbreaks have shown that the hemagglutinin-esterase (HE) genes of the viruses fall into two of the six recognized genetic lineages (represented by C/Kanagawa/1/76 and C/São Paulo/378/82), with there being significant genetic drift compared to earlier circulating viruses within both lineages. The location of a number of encoded amino acid substitutions in hemagglutinin-esterase fusion (HEF) glycoproteins suggests that antigenic drift may also have occurred. Observations of ICV outbreaks in other countries, with some of the infections being associated with severe disease, indicates that ICV infection has the potential to have significant clinical and health care impacts in humans.IMPORTANCE Influenza C virus infection of humans is common, and reinfection can occur throughout life. While symptoms are generally mild, severe disease cases have been reported, but knowledge of the virus is limited, as little systematic surveillance for influenza C virus is conducted and the virus cannot be studied by classical virologic methods because it cannot be readily isolated in laboratories. A combination of systematic surveillance in Hong Kong SAR, China, and new gene sequencing methods has been used in this study to assess influenza C virus evolution and provides evidence for a 2-year cycle of disease outbreaks. The results of studies like that reported here are key to developing an understanding of the impact of influenza C virus infection in humans and how virus evolution might be associated with epidemics.

Implementation and evaluation of the human papillomavirus (HPV) vaccination pilot for men who have sex with men (MSM), England, April 2016 to March 2017.

BACKGROUND: Opportunistic human papillomavirus (HPV) vaccination for men who have sex with men (MSM) was piloted in sexual health clinics (SHC) in England between 2016 and 2018. AIM: to evaluate the pilot's first year (April 2016-March 2017) in terms of feasibility, acceptability, uptake, impact and equity and interpret the outcome in the context of wide HPV vaccination policy. METHODS: Attendance and uptake data from routine SHC surveillance datasets and a cross-sectional survey administered to individuals receiving the vaccine were analysed. RESULTS: Among 18,875 eligible MSM, 8,580 (45.5%) were recorded as having received one HPV vaccine dose, decreasing slightly with increasing age, and uptake was higher in rural than urban areas. Survey results suggested that of those receiving the first dose of HPV vaccine, 8% were new attendees and that among those, less than 11% attended just to receive the vaccine. Of those having their first HPV vaccination, 95% indicated they would like to receive the next vaccine doses at the same clinic and 85% of patients reported accessing other services when visiting SHC for the first dose of vaccine. CONCLUSION: An opportunistic HPV vaccination programme for MSM can be delivered in an acceptable and, as far as can be evaluated, equitable manner, without major disruption to SHC and HIV clinics.

Japanese Encephalitis Virus Transmitted Via Blood Transfusion, Hong Kong, China.

Japanese encephalitis virus (JEV) is a mosquitoborne virus endemic to China and Southeast Asia that causes severe encephalitis in <1% of infected persons. Transmission of JEV via blood transfusion has not been reported. We report transmission of JEV via blood donation products from an asymptomatic viremic donor to 2 immunocompromised recipients. One recipient on high-dose immunosuppressive drugs received JEV-positive packed red blood cells after a double lung transplant; severe encephalitis and a poor clinical outcome resulted. JEV RNA was detected in serum, cerebrospinal fluid, and bronchoalveolar lavage fluid specimens. The second recipient had leukemia and received platelets after undergoing chemotherapy. This patient was asymptomatic; JEV infection was confirmed in this person by IgM seroconversion. This study illustrates that, consistent with other pathogenic flaviviruses, JEV can be transmitted via blood products. Targeted donor screening and pathogen reduction technologies could be used to prevent transfusion-transmitted JEV infection in highly JEV-endemic areas.

Corynebacterium kroppenstedtii Is an Emerging Cause of Mastitis Especially in Patients With Psychiatric Illness on Antipsychotic Medication.

This retrospective study of patients with Corynebacterium kroppenstedtii infections revealed a predominance of mastitis and a potential association with psychiatric illnesses. At least one third of our patients with C kroppenstedtii mastitis had psychiatric illness, and >92% received antipsychotic medications. Drug-induced hyperprolactinemia may be an important modifiable risk factor in these patients.

A systematic review on tobacco use among civilian populations affected by armed conflict.

OBJECTIVE: To systematically examine evidence on tobacco use among conflict-affected civilian populations. DATA SOURCES: Primary quantitative and qualitative studies published in English up to April 2014. Bibliographic databases searched were EMBASE, Global Health, MEDLINE, PsycEXTRA, PsycINFO, Web of Science, Cochrane; with the main terms of: (Smoke*, tobacco*, cigarette*, nicotine, beedi, bidi, papirosi, dip, chew, snuff, snus, smokeless tobacco) AND (armed-conflict, conflict-affected, conflict, war, refugee, internally displaced, forcibly displaced, asylum, humanitarian). Grey literature was searched using humanitarian databases, websites and search engines. STUDY SELECTION: Studies were independently selected by two reviewers, with a study outcome of tobacco use and a population of conflict-affected civilian populations such as internally displaced persons, refugees, residents in conflict-affected areas, residents and returning forcibly displaced populations returning in stabilised and postconflict periods. 2863 studies were initially identified. DATA EXTRACTION: Data were independently extracted. The Quality Assessment Tool for Quantitative Studies and the Critical Appraisal Skills Programme for qualitative studies were used to assess study quality. DATA SYNTHESIS: 39 studies met inclusion criteria and descriptive analysis was used. Findings were equivocal on the effect of conflict on tobacco use. Evidence was clearer on associations between post-traumatic stress and other mental disorders with nicotine dependence. However, there were too few studies for definitive conclusions. No study examined the effectiveness of tobacco-related interventions. The quantitative studies were moderate (N=13) or weak (N=22) quality, and qualitative studies were moderate (N=3) or strong (N=2). CONCLUSIONS: Some evidence indicates links between conflict and tobacco use but substantially more research is required.

A novel psittacine adenovirus identified during an outbreak of avian chlamydiosis and human psittacosis: zoonosis associated with virus-bacterium coinfection in birds.

Chlamydophila psittaci is found worldwide, but is particularly common among psittacine birds in tropical and subtropical regions. While investigating a human psittacosis outbreak that was associated with avian chlamydiosis in Hong Kong, we identified a novel adenovirus in epidemiologically linked Mealy Parrots, which was not present in healthy birds unrelated to the outbreak or in other animals. The novel adenovirus (tentatively named Psittacine adenovirus HKU1) was most closely related to Duck adenovirus A in the Atadenovirus genus. Sequencing showed that the Psittacine adenovirus HKU1 genome consists of 31,735 nucleotides. Comparative genome analysis showed that the Psittacine adenovirus HKU1 genome contains 23 open reading frames (ORFs) with sequence similarity to known adenoviral genes, and six additional ORFs at the 3' end of the genome. Similar to Duck adenovirus A, the novel adenovirus lacks LH1, LH2 and LH3, which distinguishes it from other viruses in the Atadenovirus genus. Notably, fiber-2 protein, which is present in Aviadenovirus but not Atadenovirus, is also present in Psittacine adenovirus HKU1. Psittacine adenovirus HKU1 had pairwise amino acid sequence identities of 50.3-54.0% for the DNA polymerase, 64.6-70.7% for the penton protein, and 66.1-74.0% for the hexon protein with other Atadenovirus. The C. psittaci bacterial load was positively correlated with adenovirus viral load in the lung. Immunostaining for fiber protein expression was positive in lung and liver tissue cells of affected parrots, confirming active viral replication. No other viruses were found. This is the first documentation of an adenovirus-C. psittaci co-infection in an avian species that was associated with a human outbreak of psittacosis. Viral-bacterial co-infection often increases disease severity in both humans and animals. The role of viral-bacterial co-infection in animal-to-human transmission of infectious agents has not received sufficient attention and should be emphasized in the investigation of disease outbreaks in human and animals.

Look-back investigation of a health care worker infected with human immunodeficiency virus.

We report the referral of an HIV-infected surgeon and a subsequent first-ever recommended look-back investigation in Hong Kong. Efficient coordination and effective implementation of the look-back investigation yielded a high response rate of 92.3% of priority patients, with none tested HIV positive. Our experience reconfirmed the very small risk of provider-to-patient HIV transmission and the crucial importance of infection control.

Antimicrobial resistance among uropathogens that cause acute uncomplicated cystitis in women in Hong Kong: a prospective multicenter study in 2006 to 2008.

A prospective multicenter study was conducted to assess the epidemiology of antimicrobial resistance among uropathogens causing uncomplicated cystitis. Adult women with clinical diagnosis of uncomplicated cystitis were enrolled from 54 participating centers distributed all over Hong Kong during 2006 to 2008. A positive urine culture was found in 59.5% (352/592) patients. The patients had mean age of 44.9 years, and most (89.2%) were otherwise healthy. The most prevalent causative organism was Escherichia coli (77%), followed by other Enterobacteriaceae (14.2%), staphylococci (5.1%), and other Gram-positive bacteria (3.7%). The resistance rates of E. coli to co-trimoxazole and ciprofloxacin were 29.5% and 12.9%, respectively, and 14 isolates (5.2%) were confirmed as extended-spectrum beta-lactamase (ESBL) producers. Of the ESBL producers, molecular studies showed CTX-M-14, CTX-M-24, or CTX-M-9. Nitrofurantoin and fosfomycin were active against >90% of the isolates, regardless of resistance phenotypes for other drugs. Pulsed-field gel electrophoresis of representative isolates showed that the antibiotic-resistant strains were genetically diverse. Patients with history of recent antibiotic use were significantly more likely to have infection by E. coli with co-trimoxazole resistance (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.4-5.7; P = 0.003) and ciprofloxacin resistance (OR, 2.5; 95% CI, 1.1-5.8; P = 0.03). Knowledge of the resistance data and risk factors could inform better use of antibiotics for empiric therapy for acute uncomplicated cystitis.

Acute fulminant subacute sclerosing panencephalitis with absent measles and PCR studies in cerebrospinal fluid.

This report describes an atypical case of rapidly progressive subacute sclerosing panencephalitis presenting as transient visual agnosia and myoclonus in a 14-year-old male. There were no typical periodic complexes in serial electroencephalographic monitoring; cerebrospinal fluid measles antibody titer was negative. The diagnosis was made by molecular and histologic examination of open brain biopsy tissue.