Candida parapsilosis infection in very low birthweight infants

In a UK national surveillance study, we found that Candida parapsilosis accounted for one quarter of all cases of invasive fungal infection in very low birthweight infants. C parapsilosis was associated with fewer deep-seated infections than C albicans, but mortality was similar. Ongoing surveillance is needed to monitor the epidemiology of invasive fungal infection in very low birthweight infants.This study was partly supported by an educational grant provided by Pfizer UK

Enhanced nasopharyngeal infection and shedding associated with an epidemic lineage of emm3 group A Streptococcus

Background: A group A Streptococcus (GAS) lineage of genotype emm3, sequence type 15 (ST15) was associated with a six month upsurge in invasive GAS disease in the UK. The epidemic lineage (Lineage C) had lost two typical emm3 prophages, Φ315.1 and Φ315.2 associated with the superantigen ssa, but gained a different prophage (ΦUK-M3.1) associated with a different superantigen, speC and a DNAse spd1. Methods and Results: The presence of speC and spd1 in Lineage C ST15 strains enhanced both in vitro mitogenic and DNAse activities over non-Lineage C ST15 strains. Invasive disease models in Galleria mellonella and SPEC-sensitive transgenic mice, revealed no difference in overall invasiveness of Lineage C ST15 strains compared to non-Lineage C ST15 strains, consistent with clinical and epidemiological analysis. Lineage C strains did however markedly prolong murine nasal infection with enhanced nasal and airborne shedding compared to non-Lineage C strains. Deletion of speC or spd1 in two Lineage C strains identified a possible role for spd1 in airborne shedding from the murine nasopharynx. Conclusions: Nasopharyngeal infection and shedding of Lineage C strains was enhanced compared to nonLineage C strains and this was, in part, mediated by the gain of the DNase spd1 through prophage acquisition

Turner et al. Reply to "Emergence of the Same Successful Clade among Distinct Populations of emm89 Streptococcus pyogenes in Multiple Geographic Regions"

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Household transmission of invasive group A Streptococcus infections in England: a population-based study, 2009, 2011 to 13

Invasive group A s treptococcal infection has a 15% case fatality rate and a risk of secondary transmission. This retrospective study us ed two national data sources from England ; enhanced surveillance ( 2009) and a case management system ( 2011 - 13) to identify clusters of sever e group A streptococcal disease . 2 4 household pairs were identified. The median onset interval between cases was 2 days (range 0 - 28) with simultaneous onset in 8 pairs . The attack rate during the 30 days after first exposure to a primary case was 4 52 0 per 100000 person - years at risk (95% CI 2 900 - 673 0 ) a 19 40 ( 12 40 - 28 80 ) fold elevation over the background incidence . The theoretical number needed to treat ( NNT ) to prevent one secondary case using antibiotic prophylaxis was 2 71 ( 194 - 454 ) overall, 50 for mother - neonate pairs ( 2 7 - 3 93 ) and 8 2 for couples aged 75 years and over ( 46 - 417 ). Whilst a dramatic increased risk of infection was noted in all household contacts, increased ris k was greatest for mother - neonate pairs and couples aged 75 and over , suggesting targeted prophylaxis c ould be considered. Offering prophylaxis is challenging due to the short time interval between cases emphasising the importance of immediate notification and assessment of contacts

Emerging invasive group A Streptococcus M1UK lineage detected by allele-specific PCR, England, 2020

Increasing reports of invasive Streptococcus pyogenes infections mandate surveillance for toxigenic lineage M1UK. An allele-specific PCR was developed to distinguish M1UK from other emm1 strains. The M1UK lineage represented 91% of invasive emm1 isolates in England in 2020. Allele-specific PCR will permit surveillance for M1UK without need for genome sequencing

Epidemiology of Confirmed COVID-19 Deaths in Adults, England, March-December 2020

Of the 58,186 coronavirus deaths among adults in England during March-December 2020, 77% occurred in hospitals, 93% were in patients >60 years, and 91% occurred within 28 days of positive specimen. Cumulative mortality rates were highest among persons of Black, Asian, other, or mixed ethnicities and in socioeconomically deprived areas

Outcome of a screening programme for the prevention of neonatal invasive early-onset group B Streptococcus infection in a UK maternity unit: an observational study

ABSTRACT Background: Against a background of failure to prevent neonatal invasive early-onset group B Streptococcus infections (GBS) in our maternity unit using risk-based approach for intrapartum antibiotic prophylaxis, we introduced an antenatal GBS carriage screening programme to identify additional women to target for prophylaxis. Objectives: To describe the implementation and outcome of an antepartum screening programme for prevention of invasive early-onset GBS infection in a UK maternity unit. Design: Observational study of outcome of screening programme intervention) with comparison to historical controls ( pre-intervention). Setting: Hospital and community-based maternity services provided by Northwick Park and Central Middlesex Hospitals in North West London. Participants: Women who gave birth between March 2014 and December 2015 at Northwick Park Hospital. Methods: Women were screened for GBS at 35–37 weeks and carriers offered intrapartum antibiotic prophylaxis. Screening programme was first introduced in hospital (March 2014) and then in community (August 2014). Compliance was audited by review of randomly selected case records. Invasive early-onset GBS infections were defined through GBS being cultured from neonatal blood, cerebrospinal fluid or sterile fluids within 0–6 days of birth. Main outcome: Incidence of early-onset GBS infections. Results: 6309 (69%) of the 9098 eligible women were tested. Screening rate improved progressively from 42% in 2014 to 75% in 2015. Audit showed that 98% of women accepted the offer of screening. Recto-vaginal GBS carriage rate was 29.4% (1822/6193). All strains were susceptible to penicillin but 11.3% (206/1822) were resistant to clindamycin. Early onset GBS rate fell from 0.99/1000 live births (25/25276) in the pre-screening period to 0.33/1000 in the screening period (Rate Ratio=0.33; p=0.08). In the subset of mothers actually screened, the rate was 0.16/1000 live births (1/6309), (Rate Ratio=0.16; p<0.05). Conclusions: Our findings confirm that an antenatal screening programme for prevention of early-onset GBS infection can be implemented in a UK maternity setting and is associated with a fall in infection rates

Characterization of emergent toxigenic M1UK Streptococcus pyogenes and associated sublineages

Streptococcus pyogenes genotype emm1 is a successful, globally distributed epidemic clone that is regarded as inherently virulent. An emm1 sublineage, M1UK, that produces increased levels of SpeA toxin was associated with increased scarlet fever and invasive infections in England in 2015/2016. Defined by 27 SNPs in the core genome, M1UK is now dominant in England. To more fully characterize M1UK, we undertook comparative transcriptomic and proteomic analyses of M1UK and contemporary non-M1UKemm1 strains (M1global). Just seven genes were differentially expressed by M1UK compared with contemporary M1global strains. In addition to speA, five genes in the operon that includes glycerol dehydrogenase were upregulated in M1UK (gldA, mipB/talC, pflD, and phosphotransferase system IIC and IIB components), while aquaporin (glpF2) was downregulated. M1UK strains have a stop codon in gldA. Deletion of gldA in M1global abrogated glycerol dehydrogenase activity, and recapitulated upregulation of gene expression within the operon that includes gldA, consistent with a feedback effect. Phylogenetic analysis identified two intermediate emm1 sublineages in England comprising 13/27 (M113SNPs) and 23/27 SNPs (M123SNPs), respectively, that had failed to expand in the population. Proteomic analysis of invasive strains from the four phylogenetic emm1 groups highlighted sublineage-specific changes in carbohydrate metabolism, protein synthesis and protein processing; upregulation of SpeA was not observed in chemically defined medium. In rich broth, however, expression of SpeA was upregulated ~10-fold in both M123SNPs and M1UK sublineages, compared with M113SNPs and M1global. We conclude that stepwise accumulation of SNPs led to the emergence of M1UK. While increased expression of SpeA is a key indicator of M1UK and undoubtedly important, M1UK strains have outcompeted M123SNPs and other emm types that produce similar or more superantigen toxin. We speculate that an accumulation of adaptive SNPs has contributed to a wider fitness advantage in M1UK on an inherently successful emm1 streptococcal background

Neurodevelopmental Impairment in Children After Group B Streptococcal Disease Worldwide: Systematic Review and Meta-analyses.

BACKGROUND: Survivors of infant group B streptococcal (GBS) disease are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified. This is the 10th of 11 articles estimating the burden of GBS disease. Here we aimed to estimate NDI in survivors of infant GBS disease. METHODS: We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data on the risk of NDI after invasive GBS disease in infants <90 days of age. We did meta-analyses to derive pooled estimates of the percentage of infants with NDI following GBS meningitis. RESULTS: We identified 6127 studies, of which 18 met eligibility criteria, all from middle- or high-income contexts. All 18 studies followed up survivors of GBS meningitis; only 5 of these studies also followed up survivors of GBS sepsis and were too few to pool in a meta-analysis. Of meningitis survivors, 32% (95% CI, 25%-38%) had NDI at 18 months of follow-up, including 18% (95% CI, 13%-22%) with moderate to severe NDI. CONCLUSIONS: GBS meningitis is an important risk factor for moderate to severe NDI, affecting around 1 in 5 survivors. However, data are limited, and we were unable to estimate NDI after GBS sepsis. Comparability of studies is difficult due to methodological differences including variability in timing of clinical reviews and assessment tools. Follow-up of clinical cases and standardization of methods are essential to fully quantify the total burden of NDI associated with GBS disease, and inform program priorities