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Background The controversial hypothesis that recalled immunological memory limits responses to variant virus strains has been revived by recent reports linking poor vaccine effectiveness against A(H3N2) influenza viruses with prior vaccination. The impact of memory induced by prior infection is rarely considered, and is difficult to ascertain because infections are often sub-clinical. This study investigates influenza vaccine immunogenicity among participants who had been monitored for 9 years for clinical influenza infection or seroconversion. Methods In 2007, 269 households from Ha Nam, Viet Nam commenced ongoing monitoring for influenza infection. In 2016, 72 adult participants with documented prior A(H3N2) infection and 28 without infection received trivalent inactivated influenza vaccine for the first time. Serological responses were assessed by hemagglutination inhibition assay against 40 A(H3N2) viruses spanning 1968-2018. Effects of prior infection were determined by comparing geometric mean titres and titre rises. Generalized additive and lowess models were used to fit, and compare, titre landscapes across strains. Findings Participants with documented prior A(H3N2) virus infection had higher pre-vaccine titres against strains circulating since 2004 compared to those without prior infection. Moreover, they had higher titre rises on days 7, 14, 21 and 280 post-vaccination against vaccine and subsequently circulating strains. Accordingly, 1/72 versus 4/28 of vaccinees with and without documented prior infection experienced illness due to A(H3N2) in the season after vaccination (p = 0.021). The range of A(H3N2) virus clades recognized by vaccine-induced antibodies was associated with the clade that last caused infection, indicating that recalled immunity drove antibody production against shared epitopes. Interpretation These results suggest that immunological memory from prior infection drives and shapes antibody production induced by inactivated influenza vaccine, and underpins the capacity for vaccine to induce sufficient antibody for protection.

Aims and Objective: 1-Alkynes are the important precursors for the CuAAC click chemistry. The hybrid of 1,2,3-triazole ring to the chromene ring and sugar moiety could bring some remarkable biological properties. Propargyl derivatives are usually used in the click chemistry. This article reported the synthesis of 2-amino-4-aryl-7-propargyloxy-4-aryl-4H-chromene-3-carbonitriles using propargyl bromide as alkylation agent and the use of potassium carbonate and sodium hydride as bases in the conversion of 2-amino-4-aryl-7- hydroxy-4-aryl-4H-chromene-3-carbonitriles into corresponding propargyl ethers in Williamson’s ether synthesis. Materials and Methods: The use of CTAB for the synthesis of benzylidene malononitriles and anhydrous potassium carbonate as a catalyst in absolute ethanol in the synthesis of 2-amino-7-hydroxy-4H-chromene-3- carbonitriles is an efficient and simple synthetic method. Propargyl ether compounds of these 4H-chromene-3- carbonitriles were obtained from the alkylation reaction by propargyl bromide. Two procedures were applied: K2CO3 as a base in acetone solvent (Procedure A) and NaH as a base in DMF solvent (Procedure B). The single-crystal X-ray structure of propargyl ether 5e has been studied. Results: The use of K2CO3 and NaH as bases in the Williamson’s ether synthesis from 2-amino-7-hydroxy-4Hchromene- 3-carbonitriles showed that Procedure B was the better route and gave ethers in the higher yields. 2- Amino-4-aryl-7-propargyloxy-4-aryl-4H-chromene-3-carbonitriles were obtained from corresponding 7- hydroxy-4H-chromene-3-carbonitriles. Yields of ethers 5a-i were 70−89% and 80−96%, respectively depending on the used procedures. Conclusion: The described methods are simple, clean and environmentally friendly alternatives for the preparation of 2-amino-4-aryl-7-hydroxy-4H-chromene-3-carbonitriles. The conditions for the transformation of these compounds into propargyl ethers include dried DMF as a solvent, NaH as a base and reaction time of 2 h at the room temperature. A series of 2-amino-4-aryl-7-hydroxy-4-aryl-4H-chromene-3-carbonitriles were obtained based on investigated reaction condition.

s The series of 2-amino-7-propargyloxy-4H-chromene-3-carbonitriles 5a-t were synthesized from corresponding 2-amino-7-phydroxy-4H-chromene-3-carbonitriles 4a-t and propargyl bromide. Two procedures were used in these syntheses: K2CO3/acetone and NaH/DMF procedures with yields of 65–89% and 80–96%, respectively. 1H-1,2,3-Triazole-tethered 4H-chromene− d -glucose conjugates 7a-t were synthesized using click chemistry of propargyl ethers 5a-t and tetra-O-acetyl-β- d -glucopyranosyl azide. Cu@MOF-5 was the optimal catalyst for this chemistry. The yields of 1H-1,2,3-triazoles were 80–97.8%. All triazoles 7a-t were evaluated in vitro for anti-microorganism activities. Among tested compounds with MIC values of 1.56–6.25 μM, there were four compounds against B. subtilis, four compounds against S. aureus, and four compounds against S. epidermidis; five compounds against E. coli, four compounds against K. pneumoniae, five compounds against P. aeruginosa, and six compounds against S. typhimurium. Compounds 7c,7d,7f,7h, and 7r had MIC values of 1.56–6.25 μM for three clinical MRSA isolates. Some compounds had inhibitory activities against four fungi, including A. niger, A. flavus, C. albicans, and S. cerevisiae, with MIC values of 1.56–6.25 μM. Some 1H-1,2,3-triazoles had comparatively low toxicity against RAW 264.7 cells.

A series of 2-amino-7-hydroxy-4H-chromene-3-carbonitriles 4a-l were synthesized through three-component reaction using sodium carbonate as a catalyst. The reaction was carried out in 96% ethanol-wa...

Contains fulltext : 248619.pdf (Publisher’s version ) (Closed access) Studies of successive vaccination suggest that immunological memory against past influenza viruses may limit responses to vaccines containing current strains. The impact of memory induced by prior infection is rarely considered and is difficult to ascertain, because infections are often subclinical. This study investigated influenza vaccination among adults from the Ha Nam cohort (Vietnam), who were purposefully selected to include 72 with and 28 without documented influenza A(H3N2) infection during the preceding 9 years (Australian New Zealand Clinical Trials Registry 12621000110886). The primary outcome was the effect of prior influenza A(H3N2) infection on hemagglutinin-inhibiting antibody responses induced by a locally available influenza vaccine administered in November 2016. Baseline and postvaccination sera were titrated against 40 influenza A(H3N2) strains spanning 1968-2018. At each time point (baseline, day 14 and day 280), geometric mean antibody titers against 2008-2018 strains were higher among participants with recent infection (34 (29-40), 187 (154-227) and 86 (72-103)) than among participants without recent infection (19 (17-22), 91 (64-130) and 38 (30-49)). On days 14 and 280, mean titer rises against 2014-2018 strains were 6.1-fold (5.0- to 7.4-fold) and 2.6-fold (2.2- to 3.1-fold) for participants with recent infection versus 4.8-fold (3.5- to 6.7-fold) and 1.9-fold (1.5- to 2.3-fold) for those without. One of 72 vaccinees with recent infection versus 4 of 28 without developed symptomatic A(H3N2) infection in the season after vaccination (P = 0.021). The range of A(H3N2) viruses recognized by vaccine-induced antibodies was associated with the prior infection strain. These results suggest that recall of immunological memory induced by prior infection enhances antibody responses to inactivated influenza vaccine and is important to attain protective antibody titers.

Background: Multidrug-resistant bacteria including carbapenem resistant Pseudomonas aeruginosa are recognised as an important cause of hospital-acquired infections worldwide. To determine the molecular characterisation and antibiotic resistant genes associated with carbapenem-resistant P. aeruginosa. Methods: we conducted whole-genome sequencing and phylogenetic analysis of 72 carbapenem-resistant P. aeruginosa isolated from hospital-acquired infection patients from 2010 to 2015 in three major hospitals in Hanoi, Vietnam. Results: We identified three variants of IMP genes, among which IMP-15 gene was the most frequent (n= 34) in comparison to IMP-26 (n= 2) and IMP-51 (n=12). We observed two isolates with imipenem MIC >128mg/L that co-harboured IMP-15 and DIM-1 genes and seven isolates (imipenem MIC> 128mg/L) with KPC-1 gene from the same hospital. MLST data showed that sequence types (ST) of 72 isolates were classified into 18 STs and phylogenetic tree analysis divided these isolates into nine groups. Conclusion: Our results provide evidence that not only IMP-26, but other variants of IMPs like IMP-15 and IMP-51 genes and several STs (ST235, ST244, ST277, ST310, ST773 and ST3151) have been disseminated in health care settings in Vietnam. Also, we report the first finding in Vietnam that two isolates belonging to ST1240 and ST3340 harboured two important carbapenemase genes (IMP-15 and, DIM-1) and seven isolates belonging to ST3151 of P. aeruginosa carried the KPC-1 gene, which could be a potential cause of seriously restricted available treatment options in healthcare settings.

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication., Background: In 2015, Singapore had the first and only reported foodborne outbreak of invasive disease caused by the group B Streptococcus (GBS; Streptococcus agalactiae). Disease, predominantly septic arthritis and meningitis, was associated with sequence type (ST)283, acquired from eating raw farmed freshwater fish. Although GBS sepsis is well-described in neonates and older adults with co-morbidities, this outbreak affected non-pregnant and younger adults with fewer co-morbidities, suggesting greater virulence. Before 2015 ST283 had only been reported from twenty humans in Hong Kong and two in France, and from one fish in Thailand. We hypothesised that ST283 was causing region-wide infection in Southeast Asia. Methodology/principal findings: We performed a literature review, whole genome sequencing on 145 GBS isolates collected from six Southeast Asian countries, and phylogenetic analysis on 7,468 GBS sequences including 227 variants of ST283 from humans and animals. Although almost absent outside Asia, ST283 was found in all invasive Asian collections analysed, from 1995 to 2017. It accounted for 29/38 (76%) human isolates in Lao PDR, 102/139 (73%) in Thailand, 4/13 (31%) in Vietnam, and 167/739 (23%) in Singapore. ST283 and its variants were found in 62/62 (100%) tilapia from 14 outbreak sites in Malaysia and Vietnam, in seven fish species in Singapore markets, and a diseased frog in China. Conclusions: GBS ST283 is widespread in Southeast Asia, where it accounts for a large proportion of bacteraemic GBS, and causes disease and economic loss in aquaculture. If human ST283 is fishborne, as in the Singapore outbreak, then GBS sepsis in Thailand and Lao PDR is predominantly a foodborne disease. However, whether transmission is from aquaculture to humans, or vice versa, or involves an unidentified reservoir remains unknown. Creation of cross-border collaborations in human and animal health are needed to complete the epidemiological picture., Support for this project was provided by the Molecular Biology Laboratory and the Department of Laboratory Medicine, Tan Tock Seng Hospital; by the Environmental Health Institute, National Environment Agency, Singapore; by the Ministry of Health, Singapore, through the Singapore Infectious Diseases Initiative grant number SIDI/2016/002 (TB) https://www.moh.gov.sg, and the National Medical Research Council, Ministry of Health, Singapore grant number NMRC/CIRG/1467/2017 (SLC) http://www.nmrc.gov.sg, by the UK Global Challenges Research Fund via the Scottish Funding Council, SFC/AN/10/2018 (RNZ) http://www.sfc.ac.uk, and by the Global Disease Detection program of the U.S. Centers for Disease Control and Prevention.

Background Antibiotic resistance is a major global public health threat. Antibiotic use can directly impact the antibiotic resistant genes (ARGs) profile of the human intestinal microbiome and consequently the environment through shedding. Methods We determined the resistome of human feces, animal stools, human food and environmental (rain, well, and irrigative water) samples (n = 304) in 40 households within a community cohort and related the data to antibiotic consumption. Metagenomic DNA was isolated and qPCR was used to determine presence of mobile colistin resistance (mcr) genes, genes encoding extended-spectrum β-lactamases (ESBL), carbapenemases and quinolone resistance genes. Results Nearly 40 % (39.5%, 120/304) of samples contained ESBL genes (most frequent were CTX-M-9 (23.7% [72/304]), CTX-M-1 (18.8% [57/304]). Quinolone resistance genes (qnrS) were detected in all human and 91% (41/45) of animal stool samples. Mcr-1 and mcr-3 were predominantly detected in human feces at 88% (82/93) and 55% (51/93) and animal feces at 93% (42/45) and 51% (23/45), respectively. Mcr-2, mrc-4 and mcr-5 were not detected in human feces, and only sporadically ( Conclusions Our study indicated that ARGs were abundant in human and animal stools in a rural Vietnamese community, including ARGs targeting last resort antibiotics. The resistomes of animal and human stools were similar as opposed to the resistomes from water and food sources. No association between antibiotic use and ARG profiles was found in a setting of high background rates of AMR.

Despite their classification as low pathogenicity avian influenza viruses (LPAIV), A/H9N2 viruses cause significant losses in poultry in many countries throughout Asia, the Middle East and North Africa. To date, poultry surveillance in Vietnam has focused on detection of influenza H5 viruses, and there is limited understanding of influenza H9 epidemiology and transmission dynamics. We determined prevalence and diversity of influenza A viruses in chickens from live bird markets (LBM) of 7 northern Vietnamese provinces, using pooled oropharyngeal swabs collected from October to December 2014. Screening by real time RT-PCR revealed 1207/4900 (24.6%) of pooled swabs to be influenza A virus positive; overall prevalence estimates after accounting for pooling (5 swabs/pools) were 5.8% (CI 5.4–6.0). Subtyping was performed on 468 pooled swabs with M gene Ct, Highlights • We report detection of highly pathogenic avian influenza (HPAI) from healthy chickens in Live Bird Markets of Vietnam. Because all breeds of domestic chickens are extremely susceptible to HPAI, we speculate that HPAI detections from market chickens may reflect infections that occur after arrival in the market. Alternatively, shedding of HPAI from healthy birds may reflect vaccine-induced protective immunity that mitigates disease but does not block viral infection. • As many as 49% of all pooled surveillance swabs were positive for influenza A virus, corresponding to an overall Influenza A prevalence of 5.45% (95% Confidence Interval 5.4-6.0%). • Low pathogenicity avian influenza (LPAI) H9N2 accounted for the vast majority of all influenza A detections in market chickens sampled from 9 northern provinces. • To date there is no evidence to suggest an interaction effect between circulation of H5 and H9 viruses; however sampling strategies that involve pooling of surveillance swabs from multiple birds greatly complicates the assessment of co-infection rates or evaluation of epidemiological associations.

An efficient and simple synthesis of substituted 2-amino-4H-chromene-3-carbonitriles was developed by the one-pot and three-component reaction of a mixture of corresponding substituted benzaldehydes, resorcinol, and malononitrile in the presence of sodium carbonate solution as a catalyst at room temperature.

During an outbreak of severe acute respiratory infections in 2 orphanages, Vietnam, 7/12 hospitalized children died. All hospitalized children and 26/43 children from outbreak orphanages tested positive for rhinovirus versus 9/40 control children (p = 0.0005). Outbreak rhinoviruses formed a distinct genetic cluster. Human rhinovirus is an underappreciated cause of severe pneumonia in vulnerable groups.