Background While hand, foot and mouth disease (HFMD) is primarily self-resolving—soaring incidence rate of symptomatic HFMD effectuates economic burden in the Asia-Pacific region. Singapore has seen a conspicuous rise in the number of HFMD cases from 2010s. Here, we aims to identify the serology and genotypes responsible for such outbreaks in hospitals and childcare facilities. Methods We studied symptomatic paediatric HFMD cases from 2013 to 2018 in Singapore. Surveillance for subclinical enterovirus infections was also performed in childcares at the same time period. Results Genotyping 101 symptomatic HFMD samples revealed CV-A6 as the major etiological agent for recent outbreaks. We detected infections with CV-A6 (41.0%), EV-A71 (7%), CV-A16 (3.0%), coxsackievirus A2, CV-A2 (1.0%) and coxsackievirus A10, CV-A10 (1.0%). Phylogenetic analysis of local CV-A6 strains revealed a high level of heterogeneity compared against others worldwide, dissimilar to other HFMD causative enteroviruses for which the dominant strains and genotypes are highly region specific. We detected sub-clinical enterovirus infections in childcare centres; 17.1% (n = 245) tested positive for enterovirus in saliva, without HFMD indicative symptoms at the point of sample collection. Conclusions CV-A6 remained as the dominant HFMD causative strain in Singapore. Silent subclinical enteroviral infections were detected and warrant further investigations.
While the underlying determinants are unclear, hand, foot and mouth disease (HFMD) presents a wide spectrum of clinical manifestations with varying severity in different individuals. Recently, many studies identified the human microbiome as a critical factor in the pathogenesis of various diseases. Therefore, we here investigated the ecological dynamics of the oral microbiome changes during the HFMD infection. After targeted enrichment of all known vertebrate viruses, the virome profiles of symptomatic and asymptomatic HFMD patients were examined and revealed to be significantly altered from those of healthy individuals, with nine discriminative viruses detected. Further characterization of the prokaryotic microbiome revealed an elevated level of Streptococcus sp. as the most important signature of the symptomatic HFMD cohort, positively correlating to the level of enterovirus A RNA. In addition, we found that while coxsackievirus A5 is detected in saliva RNA of all asymptomatic cases, coxsackievirus A6 dominates the majority of the symptomatic cohort.
Dengue is a mosquito-borne flavivirus that causes 21,000 deaths annually. Depsides and depsidones of lichens have previously been reported to be antimicrobials. In this study, our objective was to identify lichen-derived depsides and depsidones as dengue virus inhibitors. The 18 depsides and depsidones of Usnea baileyi, Usnea aciculifera, Parmotrema dilatatum, and Parmotrema tsavoense were tested against dengue virus serotype 2. Two depsides and one depsidone inhibited dengue virus serotype 2 without any apparent cytotoxicity. Diffractaic acid, barbatic acid, and Parmosidone C were three active compounds further characterized for their efficacies (EC50), cytotoxicities (CC50), and selectivity index (SI; CC50/EC50). Their EC50 (SI) values were 2.43 ± 0.19 (20.59), 0.91 ± 0.15 (13.33), and 17.42 ± 3.21 (8.95) μM, respectively. Diffractaic acid showed the highest selectivity index, and similar efficacies were also found in dengue serotypes 1–4, Zika, and chikungunya viruses. Cell-based studies revealed that the target was mainly in the late stage with replication and the formation of infectious particles. This report highlights that a lichen-derived diffractaic acid could become a mosquito-borne antiviral lead as its selectivity indices ranged from 8.07 to 20.59 with a proposed target at viral replication.
Dear Editor,Extended-spectrum beta-lactamases (ESBLs) are rapidly expanding groups of enzymes that can hydrolyse the majority of beta-lactam antibiotics with the exception of carbapenems, and are inhibited by clavulanic acid. 1 They are commonly found on plasmids, which are extra-chromosomal deoxyribonucleic acid (DNA) that can transfer between bacteria. ESBL-producing Enterobacteriaeceae (ESBL-E) frequently cause infections in Singapore hospitals, and have increased rapidly since the 1990s to approximately 20% and 35% of all Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) clinical isolates respectively. 2 ESBL-E carriage and infection rates in the community setting have increased globally since the 1990s. 3 In Singapore, 6.3% of emergency department attendees in 2006 with no previous healthcare contact were ESBL-E carriers-unfortunately, there has been no follow-up study. 4 It is postulated that the rise in community-associated ESBL-E carriage and infection rates is due to cross-species transmission from food-producing animals, particularly poultry. 3,5,6 Numerous studies have shown high rates of ESBL-E in chickens around the world. 3,[6][7][8] Citing the Agri-Food and Veterinary Authority of Singapore (AVA), a 2013 news report stated that Singapore imported approximately 500 tons of chicken a day, of which 78.8% came from Brazil (205 tons) and Malaysia (189 tons). 9 We performed a cross-sectional survey on 26 chicken breast samples over a period of 4 months (May 2015 to August 2015) in an attempt to determine the prevalence of ESBL-E in chicken meat in Singapore, and to determine if there was a difference in ESBL-E carriage between raw and commercially cooked chicken.Raw chilled and frozen meat were obtained from various wet markets, supermarkets, and online shops (n = 19), whereas cooked samples were obtained from fast food restaurants and hawker centres (n = 7). Samples were labelled as "antibiotic-free" if this was indicated on the packaging. The country of origin was obtained from the packaging label, or from the seller in the case of wet market samples.Samples were processed under aseptic conditions within 4 hours of collection. Approximately 25 grams of breast Annals Academy of Medicine
During the period from late 2019 to early 2020, we performed a foodborne virus detection from shellfish collected in Singapore at retail level. Multiple human enteric viruses were included as our targets including human noroviruses (NoVs) GI and GII, hepatitis A virus, hepatitis E virus and rotavirus. Out of the 60 shellfish samples, 23 (38·3%) were detected to be positive by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) with human enteric viruses. Six samples were selected to proceed with virome capture sequencing with positive control samples spiked with serially diluted NoV GII clinical samples in oyster extract. As a result, the natural sample with comparable Ct values (34·0–35·0) of the spiked sample as detected by RT‐qPCR generated much lower read counts (>7‐log2 cumulative sum scaling difference) and genome coverage (406 nt. vs 3715 nt.), suggesting that the RT‐qPCR positive signals detected from the shellfish samples collected at the retail market were likely from degraded RNA derived from inactive virus particles.
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