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Studies on the microbial communities in non-human primate hosts provide unique insights in both evolution and function of microbes related to human health and diseases. Using 16S rRNA gene amplicon profiling, we examined the oral, anal and vaginal microbiota in a group of non-captive rhesus macaques (N = 116) and compared the compositions with the healthy communities from Human Microbiome Project. The macaque microbiota was dominated by Bacteroidetes, Firmicutes and Proteobacteria; however, there were marked differences in phylotypes enriched across body sites indicative of strong niche specialization. Compared to human gut microbiota where Bacteroides predominately enriched, the surveyed macaque anal community exhibited increased abundance of Prevotella. In contrast to the conserved human vaginal microbiota extremely dominated by Lactobacillus, the macaque vaginal microbial composition was highly diverse while lactobacilli were rare. A constant decrease of the vaginal microbiota diversity was observed among macaque samples from juvenile, adult without tubectomy, and adult with tubectomy, with the most notable distinction being the enrichment of Halomonas in juvenile and Saccharofermentans in contracepted adults. Both macaque and human oral microbiota were colonized with three most common oral bacterial genera: Streptococcus, Haemophilus and Veillonella, and shared relatively conserved communities to each other. A number of bacteria related to human pathogens were consistently detected in macaques. The findings delineate the range of structure and diversity of microbial communities in a wild macaque population, and enable the application of macaque as an animal model for future characterization of microbes in transmission, genomics and function.

The World Health Organization selects influenza vaccine compositions biannually to cater to peaks in temperate regions. In tropical and subtropical regions, where influenza seasonality varies and epidemics can occur year-round, the choice of vaccine remains uncertain. Our 17-year molecular epidemiologic survey showed that most influenza A(H3N2) (9/11) and B (6/7) vaccine strains had circulated in East Asia >1 year before inclusion into vaccines. Northern Hemisphere vaccine strains and circulating strains in East Asia were closely matched in 7 (20.6%) of 34 seasons for H3N2 and 5 (14.7%) of 34 seasons for B. Southern Hemisphere vaccines also had a low probability of matching (H3N2, 14.7%; B, 11.1%). Strain drift among seasons was common (H3N2, 41.2%; B, 35.3%), and biannual vaccination strategy (Northern Hemisphere vaccines in November followed by Southern Hemisphere vaccines in May) did not improve matching. East Asia is an important contributor to influenza surveillance but often has mismatch between vaccine and contemporarily circulating strains.

Summary IFITM3 and TLR3 SNPs are associated with fatal clinical outcome of Chinese patients with avian (H7N9) or pandemic (H1N1pdm09) influenza virus infections, and the risks are cumulative. Our findings pose important public health and clinical implications in the at-risk populations., Background. We examined associations between single-nucleotide polymorphisms (SNPs) of IFITM3, TLR3, and CD55 genes and influenza clinical outcomes in Chinese. Methods. A multicenter study was conducted on 275 adult cases of avian (H7N9) and pandemic (H1N1pdm09) influenza. Host DNA was extracted from diagnostic respiratory samples; IFITM3 rs12252, TLR3 rs5743313, CD55 rs2564978, and TLR4 rs4986790/4986791 were targeted for genotyping (Sanger sequencing). The primary outcome analyzed was death. Results. IFITM3 and TLR3 SNPs were in Hardy–Weinberg equilibrium; their allele frequencies (IFITM3/C-allele 0.56, TLR3/C-allele 0.88) were comparable to 1000 Genomes Han Chinese data. We found over-representation of homozygous IFITM3 CC (54.5% vs 33.2%; P = .02) and TLR3 CC (93.3% vs 76.9%; P = .04) genotypes among fatal cases. Recessive genetic models showed their significant independent associations with higher death risks (adjusted hazard ratio [aHR] 2.78, 95% confidence interval [CI] 1.29–6.02, and aHR 4.85, 95% CI 1.11−21.06, respectively). Cumulative effects were found (aHR 3.53, 95% CI 1.64−7.59 per risk genotype; aHR 9.99, 95% CI 1.27−78.59 with both). Results were consistent for each influenza subtype and other severity indicators. The CD55 TT genotype was linked to severity. TLR4 was nonpolymorphic. Conclusions. Host genetic factors may influence clinical outcomes of avian and pandemic influenza infections. Such findings have important implications on disease burden and patient care in at-risk populations.

Influenza is a major cause of severe respiratory infections leading to excessive hospitalizations and deaths globally; annual epidemics, pandemics, and sporadic/endemic avian virus infections occur as a result of rapid, continuous evolution of influenza viruses. Emergence of antiviral resistance is of great clinical and public health concern. Currently available antiviral treatments include four neuraminidase inhibitors (oseltamivir, zanamivir, peramivir, laninamivir), M2-inibitors (amantadine, rimantadine), and a polymerase inhibitor (favipiravir). In this review, we focus on resistance issues related to the use of neuraminidase inhibitors (NAIs). Data on primary resistance, as well as secondary resistance related to NAI exposure will be presented. Their clinical implications, detection, and novel therapeutic options undergoing clinical trials are discussed.

BACKGROUND: The development of a vaccine for norovirus requires a detailed understanding of global genetic diversity of noroviruses. We analysed their epidemiology and diversity using surveillance data from the NoroNet network.METHODS: We included genetic sequences of norovirus specimens obtained from outbreak investigations and sporadic gastroenteritis cases between 2005 and 2016 in Europe, Asia, Oceania, and Africa. We genotyped norovirus sequences and analysed sequences that overlapped at open reading frame (ORF) 1 and ORF2. Additionally, we assessed the sampling date and country of origin of the first reported sequence to assess when and where novel drift variants originated.FINDINGS: We analysed 16 635 norovirus sequences submitted between Jan 1, 2005, to Nov 17, 2016, of which 1372 (8·2%) sequences belonged to genotype GI, 15 256 (91·7%) to GII, and seven (INTERPRETATION: Continuous changes in the global norovirus genetic diversity highlight the need for sustained global norovirus surveillance, including assessment of possible immune escape and evolution by recombination, to provide a full overview of norovirus epidemiology for future vaccine policy decisions.FUNDING: European Union's Horizon 2020 grant COMPARE, ZonMw TOP grant, the Virgo Consortium funded by the Dutch Government, and the Hungarian Scientific Research Fund.

Background The epidemiology of human parechovirus (HPeV) in Asia remains obscure. We elucidated the prevalence, seasonality, type distribution and clinical presentation of HPeV among children in Hong Kong. Methods A 24-month prospective study to detect HPeV in children ≤36 months hospitalized for acute viral illnesses. Results 2.3% of the 3911 children examined had HPeV infection, with most (87.5%) concentrated in September-January (autumn-winter). 81.3% were HPeV1 and 12.5% were HPeV4, while HPeV3 was rare (2.5%). HPeV was a probable cause of the disease in 47.7% (42/88), mostly self-limiting including acute gastroenteritis, upper respiratory tract infection and maculopapular rash. A neonate developed severe sepsis-like illness with HPeV3 as the only pathogen detected. A high proportion (60.0%) of children coinfected with HPeV and other respiratory virus(es) had acute bronchiolitis or pneumonia. Six children with HPeV coinfections developed convulsion / pallid attack. Most rash illnesses exhibited a generalized maculopapular pattern involving the trunk and limbs, and were more likely associated with HPeV4 compared to other syndrome groups (36.4% vs. 3.1%, p = 0.011). Conclusions In Hong Kong, HPeV exhibits a clear seasonality (autumn-winter) and was found in a small proportion (2.3%) of young children (≤36 months) admitted with features of acute viral illnesses. The clinical presentation ranged from mild gastroenteritis, upper respiratory tract infection and febrile rash to convulsion and severe sepsis-like illness. HPeV3, which is reported to associate with more severe disease in neonates, is rare in Hong Kong. HPeV coinfection might associate with convulsion and aggravate other respiratory tract infections.

We evaluated the acceptability of an additional ad hoc influenza vaccination among the health care professionals following seasons with significant antigenic drift. Self-administered, anonymous surveys were performed by hard copy questionnaires in public hospitals, and by an on-line platform available to all healthcare professionals, from April 1st to May 31st, 2015. A total of 1290 healthcare professionals completed the questionnaires, including doctors, nurses, and allied health professionals working in both the public and private systems. Only 31.8% of participating respondents expressed an intention to receive the additional vaccine, despite that the majority of them agreed or strongly agreed that it would bring benefit to the community (88.9%), save lives (86.7%), reduce medical expenses (76.3%), satisfy public expectation (82.8%), and increase awareness of vaccination (86.1%). However, a significant proportion expressed concern that the vaccine could disturb the normal immunization schedule (45.5%); felt uncertain what to do in the next vaccination round (66.0%); perceived that the summer peak might not occur (48.2%); and believed that the summer peak might not be of the same virus (83.5%). Furthermore, 27.8% of all respondents expected that the additional vaccination could weaken the efficacy of previous vaccinations; 51.3% was concerned about side effects; and 61.3% estimated that there would be a low uptake rate. If the supply of vaccine was limited, higher priority groups were considered to include the elderly aged ≥65 years with chronic medical conditions (89.2%), the elderly living in residential care homes (87.4%), and long-stay residents of institutions for the disabled (80.7%). The strongest factors associated with accepting the additional vaccine included immunization with influenza vaccines in the past 3 years, higher perceived risk of contracting influenza, and higher perceived severity of the disease impact. The acceptability to an additional ad hoc influenza vaccination was low among healthcare professionals. This could have a negative impact on such additional vaccination campaigns since healthcare professionals are a key driver for vaccine acceptance. The discordance in perceived risk and acceptance of vaccination regarding self versus public deserves further evaluation.

Norovirus genogroup II genotype 4 (GII.4) has been the predominant cause of viral gastroenteritis since 1996. Here we show that during the winter of 2014–2015, an emergent variant of a previously rare norovirus GII.17 genotype, Kawasaki 2014, predominated in Hong Kong and outcompeted contemporary GII.4 Sydney 2012 in hospitalized cases. GII.17 cases were significantly older than GII.4 cases. Root-to-tip and Bayesian BEAST analyses estimate GII.17 viral protein 1 (VP1) evolves one order of magnitude faster than GII.4 VP1. Residue substitutions and insertion occur in four of five inferred antigenic epitopes, suggesting immune evasion. Sequential GII.4-GII.17 infections are noted, implicating a lack of cross-protection. Virus bound to saliva of secretor histo-blood groups A, B and O, indicating broad susceptibility. This fast-evolving, broadly recognizing and probably immune-escaped emergent GII.17 variant causes severe gastroenteritis and hospitalization across all age groups, including populations who were previously less vulnerable to GII.4 variants; therefore, the global spread of GII.17 Kawasaki 2014 needs to be monitored., Norovirus GII.4 has been predominating in viral gastroenteritis for 20 years. Here the authors report the emergence and predominance of a novel fast-evolving GII.17 lineage norovirus causing viral gastroenteritis in Hong Kong, with a shift in age distribution of affected individuals towards an older age as compared to GII.4.

Background Newborns who have received hepatitis B immunization in 1980s are now young adults joining healthcare disciplines. The need for booster, pre- and post-booster checks becomes a practical question. Aims The aim of this study is to refine the HBV vaccination policy for newly admitted students in the future. Methods A prospective study on medical and nursing school entrants to evaluate hepatitis B serostatus and the response to booster doses among young adults. Findings Among 212 students, 17–23-year-old, born after adoption of neonatal immunization, 2 (0.9%) were HBsAg positive, 40 (18.9%) were anti-HBs positive. At 1 month after a single-dose booster for anti-HBs-negative students, 14.5% had anti-HBs 100 mIU/mL, respectively. The anti-HBs levels were significantly higher for females than males (mean [SD]: 431 [418] vs. 246 [339] mIU/mL, P = 0.047). At 2–4 month after the third booster dose, 97.1% had anti-HBs >100 mIU/mL and 2.9% had 10–100 mIU/mL. Conclusions Pre-booster check is still worthwhile to identify carriers among newly recruited healthcare workers born after adoption of neonatal immunization. A 3-dose booster, rather than a single dose, is required for the majority to achieve an anti-HBs level >100 mIU/mL, as memory immunity has declined in a substantial proportion of individuals. Cost-effectiveness of post-booster check for anti-HBs is low and should be further evaluated based on contextual specific utilization of results.

Human papillomavirus (HPV) genotype 52 is commonly found in Asian cases of cervical cancer but is rare elsewhere. Analysis of 611 isolates collected worldwide revealed a remarkable geographical distribution, with lineage B predominating in Asia (89.0% vs 0%-5.5%; P(corrected) < .001), whereas lineage A predominated in Africa, the Americas, and Europe. We propose that the name "Asian lineage" be used to denote lineage B, to signify this feature. Preliminary analysis suggested a higher disease risk for lineage B, although ethnogeographical confounders could not be excluded. Further studies are warranted to verify whether the reported high attribution of disease to HPV52 in Asia is due to the high prevalence of lineage B.

Objective To estimate the prevalence and attribution of two non-vaccine-covered HPV types (HPV52 and HPV58) across the world. Methods Meta-analysis on studies reported in English and Chinese between 1994 and 2012. Results The pooled prevalence and attribution rates of HPV52 and HPV58 in invasive cervical cancers were significantly higher in Eastern Asia compared to other regions (HPV52 prevalence: 5.7% vs. 1.8–3.6%, P

Human papillomavirus (HPV) 58 accounts for a notable proportion of cervical cancers in East Asia and parts of Latin America, but it is uncommon elsewhere. The reason for such ethnogeographical predilection is unknown. In our study, nucleotide sequences of E6 and E7 genes of 401 HPV58 isolates collected from 15 countries/cities across four continents were examined. Phylogenetic relationship, geographical distribution and risk association of nucleotide sequence variations were analyzed. We found that the E6 genes of HPV58 variants were more conserved than E7. Thus, E6 is a more appropriate target for type-specific detection, whereas E7 is more appropriate for strain differentiation. The frequency of sequence variation varied geographically. Africa had significantly more isolates with E6-367A (D86E) but significantly less isolates with E6-203G, -245G, -367C (prototype-like) than other regions (p ≤ 0.003). E7-632T, -760A (T20I, G63S) was more frequently found in Asia, and E7-793G (T74A) was more frequent in Africa (p < 0.001). Variants with T20I and G63S substitutions at E7 conferred a significantly higher risk for cervical intraepithelial neoplasia grade III and invasive cervical cancer compared to other HPV58 variants (odds ratio = 4.44, p = 0.007). In conclusion, T20I and/or G63S substitution(s) at E7 of HPV58 is/are associated with a higher risk for cervical neoplasia. These substitutions are more commonly found in Asia and the Americas, which may account for the higher disease attribution of HPV58 in these areas.

Avian influenza viruses pose a serious pandemic threat to humans. Better knowledge on cross-species adaptation is important. This study examined the replication and transcription efficiency of ribonucleoprotein complexes reconstituted by plasmid co-transfection between H5N1, H1N1pdm09 and H3N2 influenza A viruses, and to identify mutations in the RNA polymerase subunit that affect human adaptation. Viral RNA polymerase subunits PB1, PB2, PA and NP derived from influenza viruses were co-expressed with pPolI-vNP-Luc in human cells, and with its function evaluated by luciferase reporter assay. A quantitative RT-PCR was used to measure vRNA, cRNA, and mRNA levels for assessing the replication and transcription efficiency. Mutations in polymerase subunit were created to identify signature of increased human adaptability. H5N1 ribonucleoprotein complexes incorporated with PB2 derived from H1N1pdm09 and H3N2 viruses increased the polymerase activity in human cells. Furthermore, single amino acid substitutions at PB2 of H5N1 could affect polymerase activity in a temperature-dependent manner. By using a highly sensitive quantitative reverse transcription-polymerase chain reaction, an obvious enhancement in replication and transcription activities of ribonucleoproteins was observed by the introduction of lysine at residue 627 in the H5N1 PB2 subunit. Although less strongly in polymerase activity, E158G mutation appeared to alter the accumulation of H5N1 RNA levels in a temperature-dependent manner, suggesting a temperature-dependent mechanism in regulating transcription and replication exists. H5N1 viruses can adapt to humans either by acquisition of PB2 from circulating human-adapted viruses through reassortment, or by mutations at critical sites in PB2. This information may help to predict the pandemic potential of newly emerged influenza strains, and provide a scientific basis for stepping up surveillance measures and vaccine production.