Victoria J. Chalker

Increase in scarlet fever notifications in the United Kingdom, 2013/2014.

Increases in scarlet fever above usual seasonal levels are currently being seen across the United Kingdom. Medical practitioners have been alerted to the exceptional increase in incidence. Given the potential for this to signal a population increase in invasive group A streptococcal disease, close monitoring of invasive disease is essential.

International Mycoplasma pneumoniae typing study: interpretation of M. pneumoniae multilocus variable-number tandem-repeat analysis

Typing of Mycoplasma pneumoniae by multiple-locus variable-number tandem repeat analysis (MLVA) is increasingly in use. However, no specific internationally agreed guidance is available. Thirty M. pneumoniae DNA samples including serial dilutions of a type strain were sent to six international laboratories to perform MLVA and results were compared. Good correlation was observed, indicating that this methodology can be robustly performed in multiple sites. However, differences due to interpretation of fragment size, repeat sequence identification and repeat numbering led to inconsistency in the final profiles assigned by laboratories. We propose guidelines for interpreting M. pneumoniae MLVA typing and assigning the number of repeats.

Antibiotic Resistance among Clinical Ureaplasma Isolates Recovered from Neonates in England and Wales between 2007 and 2013

ABSTRACT Ureaplasma spp. are associated with numerous clinical sequelae with treatment options being limited due to patient and pathogen factors. This report examines the prevalence and mechanisms of antibiotic resistance among clinical strains isolated from 95 neonates, 32 women attending a sexual health clinic, and 3 patients under investigation for immunological disorders, between 2007 and 2013 in England and Wales. MICs were determined by using broth microdilution assays, and a subset of isolates were compared using the broth microdilution method and the Mycoplasma IST2 assay. The underlying molecular mechanisms for resistance were determined for all resistant isolates. Three isolates carried the tet(M) tetracycline resistance gene (2.3%; confidence interval [CI], 0.49 to 6.86%); two isolates were ciprofloxacin resistant (1.5%; CI, 0.07 to 5.79%) but sensitive to levofloxacin and moxifloxacin, while no resistance was seen to any macrolides tested. The MIC values for chloramphenicol were universally low (2 μg/ml), while inherently high-level MIC values for gentamicin were seen (44 to 66 μg/ml). The Mycoplasma IST2 assay identified a number of false positives for ciprofloxacin resistance, as the method does not conform to international testing guidelines. While antibiotic resistance among Ureaplasma isolates remains low, continued surveillance is essential to monitor trends and threats from importation of resistant clones.

Resurgence of scarlet fever in England, 2014–16: a population-based surveillance study

BACKGROUND After decades of decreasing scarlet fever incidence, a dramatic increase was seen in England beginning in 2014. Investigations were launched to assess clinical and epidemiological patterns and identify potential causes. METHODS In this population-based surveillance study, we analysed statutory scarlet fever notifications held by Public Health England from 1911 to 2016 in England and Wales to identify periods of sudden escalation of scarlet fever. Characteristics of cases and outbreaks in England including frequency of complications and hospital admissions were assessed and compared with the pre-upsurge period. Isolates from throat swabs were obtained and were emm typed. FINDINGS Data were retrieved for our analysis between Jan 1, 1911, and Dec 31, 2016. Population rates of scarlet fever increased by a factor of three between 2013 and 2014 from 8·2 to 27·2 per 100 000 (rate ratio [RR] 3·34, 95% CI 3·23-3·45; p<0·0001); further increases were observed in 2015 (30·6 per 100 000) and in 2016 (33·2 per 100 000), which reached the highest number of cases (19 206) and rate of scarlet fever notifcation since 1967. The median age of cases in 2014 was 4 years (IQR 3-7) with an incidence of 186 per 100 000 children under age 10 years. All parts of England saw an increase in incidence, with 620 outbreaks reported in 2016. Hospital admissions for scarlet fever increased by 97% between 2013 and 2016; one in 40 cases were admitted for management of the condition or potential complications. Analysis of strains (n=303) identified a diversity of emm types with emm3 (43%), emm12 (15%), emm1 (11%), and emm4 (9%) being the most common. Longitudinal analysis identified 4-yearly periodicity in population incidence of scarlet fever but of consistently lower magnitude than the current escalation. INTERPRETATION England is experiencing an unprecedented rise in scarlet fever with the highest incidence for nearly 50 years. Reasons for this escalation are unclear and identifying these remains a public health priority. FUNDING None.

Genome analysis following a national increase in Scarlet Fever in England 2014

BackgroundDuring a substantial elevation in scarlet fever (SF) notifications in 2014 a national genomic study was undertaken of Streptococcus pyogenes (Group A Streptococci, GAS) isolates from patients with SF with comparison to isolates from patients with invasive disease (iGAS) to test the hypotheses that the increase in SF was due to either the introduction of one or more new/emerging strains in the population in England or the transmission of a known genetic element through the population of GAS by horizontal gene transfer (HGT) resulting in infections with an increased likelihood of causing SF. Isolates were collected to provide geographical representation, for approximately 5% SF isolates from each region from 1st April 2014 to 18th June 2014. Contemporaneous iGAS isolates for which genomic data were available were included for comparison. Data were analysed in order to determine emm gene sequence type, phylogenetic lineage and genomic clade representation, the presence of known prophage elements and the presence of genes known to confer pathogenicity and resistance to antibiotics.Results555 isolates were analysed, 303 from patients with SF and 252 from patients with iGAS. Isolates from patients with SF were of multiple distinct emm sequence types and phylogenetic lineages. Prior to data normalisation, emm3 was the predominant type (accounting for 42.9% of SF isolates, 130/303 95%CI 37.5–48.5; 14.7% higher than the percentage of emm3 isolates found in the iGAS isolates). Post-normalisation emm types, 4 and 12, were found to be over-represented in patients with SF versus iGAS (p < 0.001). A single gene, ssa, was over-represented in isolates from patients with SF. No single phage was found to be over represented in SF vs iGAS. However, a “meta-ssa” phage defined by the presence of :315.2, SPsP6, MGAS10750.3 or HK360ssa, was found to be over represented. The HKU360.vir phage was not detected yet the HKU360.ssa phage was present in 43/63 emm12 isolates but not found to be over-represented in isolates from patients with SF.ConclusionsThere is no evidence that the increased number of SF cases was a strain-specific or known mobile element specific phenomenon, as the increase in SF cases was associated with multiple lineages of GAS.

Mycoplasma pneumoniae Epidemiology in England and Wales: A National Perspective

Investigations of patients with suspected Mycoplasma pneumoniae infection have been undertaken in England since the early 1970s. M. pneumoniae is a respiratory pathogen that is a common cause of pneumonia and may cause serious sequelae such as encephalitis and has been documented in children with persistent cough. The pathogen is found in all age groups, with higher prevalence in children aged 5–14 years. In England, recurrent epidemic periods have occurred at ~4-yearly intervals. In addition, low-level sporadic infection occurs with seasonal peaks from December to February. Voluntarily reports from regional laboratories and hospitals in England from 1975 to 2015 were collated by Public Health England for epidemiological analysis. Further data pertaining cases of note and specimens submitted to Public Health England from 2005 to 2015 for confirmation, molecular typing is included.

Development of a Multilocus Sequence Typing Scheme for Molecular Typing of Mycoplasma pneumoniae

ABSTRACT Mycoplasma pneumoniae is a major human respiratory pathogen causing both upper and lower respiratory disease in humans of all ages, and it can also result in other serious extrapulmonary sequelae. A multilocus sequence typing (MLST) scheme for M. pneumoniae was developed based on the sequences of eight housekeeping genes (ppa, pgm, gyrB, gmk, glyA, atpA, arcC, and adk) and applied to 55 M. pneumoniae clinical isolates and the two type strains M129 and FH. A total of 12 sequence types (STs) resulted for 57 M. pneumoniae isolates tested, with a discriminatory index of 0.21 STs per isolate. The MLST loci used in this scheme were shown to be stable in 10 strains following 10 sequential subculture passages. Phylogenetic analysis of concatenated sequences of the eight loci indicated two distinct genetic clusters that were directly linked to multilocus variable-number tandem repeat analysis (MLVA) type. Genetic MLST clustering was confirmed by genomic sequence analysis, indicating that the MLST scheme developed in this study is representative of the genome. Furthermore, this MLST scheme was shown to be more discriminatory than both MLVA and P1 typing for the M. pneumoniae isolates examined, providing a method for further and more detailed analysis of observed epidemic peaks of M. pneumoniae infection. This scheme is supported by a public Web-based database (http://pubmlst.org/mpneumoniae).

Seeding and Establishment of Legionella pneumophila in Hospitals: Implications for Genomic Investigations of Nosocomial Legionnaires’ Disease

Summary Whole-genome sequencing can be used to support or refute suspected links between hospital water systems and Legionnaires’ disease cases. However, caveats regarding the interpretation of genomic data from Legionella pneumophila are described that should be considered in future investigations.

Detection of macrolide resistant Mycoplasma pneumoniae in England, September 2014 to September 2015.

Mycoplasma pneumoniae infection can cause pneumonia, particularly in children. Global increase in macrolide-resistant M. pneumoniae is of concern due to limited therapeutic options. We describe the detection of macrolide resistance-conferring mutations in 9.3% of 43 clinical specimens where M. pneumoniae was detected in England and Wales from September 2014‒September 2015. This study aims to impact by highlighting the presence of macrolide resistance in M. pneumoniae positive patients, promoting increased clinical vigilance.

Integration of Genomic and Other Epidemiologic Data to Investigate and Control a Cross-Institutional Outbreak of Streptococcus pyogenes

Genomic surveillance can effectively detect such outbreaks, providing increased intelligence to support infection control.