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Technophobe
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Posted: March 08 2018 at 5:50am |
UK seeing outbreak of highly azithromycin-resistant gonorrheaMar 07, 2018 Researchers with Public Health England (PHE) are reporting sustained transmission of high-level azithromycin-resistant (HL-AziR) Neisseria gonorrhoeae infections across England, and a separate paper notes ceftriaxone-resistant gonorrhea in Australia. In a study yesterday in The Lancet Infectious Diseases, the PHE researchers report that 37 of 60 HL-AziR N gonorrhoeae isolates collected in England from November 2014 through February 2017 belonged to a single multi-antigen sequence type (ST9768). This is the same sequence type that was initially identified in seven N gonorrhoeae isolates tested when the outbreak was first identified in Leeds in 2015. When compared with 110 N gonorrhoeae isolates from the United Kingdom and Ireland with ranges of azithromycin resistance, the isolates from ST9768 clustered into three phylogenetic clades and were all found to be genetically similar, with a mean distance of 4.3 single nucleotide polymorphisms (SNPs). All of the ST9768 isolates shared a recent common ancestor indicative of recent transmission. Further analysis detected mutation 2059A→G in the 3-4 allelles of the 23S rRNA gene in almost all the HL-AziR isolates, a mutation known to be responsible for high-level azithromycin resistance. But it also detected this mutation in six of the comparator isolates from Scotland, one with low-level resistance to azithromycin and five that were susceptible. The phylogeny provides evidence that the HL-AziR isolates were descendants of the low-level azithromycin-resistant isolates, which were in turn descendants of the susceptible isolates. The authors of the study report that there was no confirmed gonorrhea treatment failure in any of these cases, most likely because the isolates were still susceptible to ceftriaxone. But the findings are a concern because azithromycin, in combination with ceftriaxone, forms the last-line of therapy for treating gonorrhea, which has become resistant to all other drugs that have been used against it. Dual therapy is recommended in England and other countries to prevent further development of resistance. Currently, the prevalence of low-level azithromycin resistant in England is 5%. But the finding that high-level azithromycin resistance can emerge from low-level resistance, the authors argue, raises the possibility that azithromycin exposure may be providing selection pressure for the emergence of high-level resistance. "Dual therapy for gonorrhea using azithromycin with ceftriaxone is clearly under threat, and we might not be able to rely on azithromycin to protect ceftriaxone," the authors write. An additional concern is that HL-AziR N gonorrhoeae has previously been observed only sporadically in England and other parts of the world, possibly because high-level azithromycin resistance might lead to fitness costs, the authors suggest. Why sustained transmission of ST9768 exists in England remains unclear. Ceftriaxone-resistant gonorrhea in AustraliaMeanwhile, in a paper yesterday in Emerging Infectious Diseases, an international team of investigators report two more instances of a clone of a ceftriaxone-resistant N gonorrhoeae strain that appears to be spreading internationally. The strain, FC428, was first identified in Japan in 2015 in a heterosexual man in his 20s. Two years later, gonococcal isolates with FC428-like susceptibility profiles (including ceftriaxone resistance) were reported in a Canadian woman and a heterosexual man from Denmark. The two newly reported cases, identified in Australia in two heterosexual men from the Philippines and China, also had a similar susceptibility profile to FC428. Phylogenetic analysis of isolates from the Japanese, Canadian, and Australian cases showed close genetic relatedness, and molecular typing demonstrated that all the strains, as well as the strain from Denmark, belonged to the same sequence type (ST1903). All cases were successfully treated, but the investigators say the findings provide new evidence that there is sustained international transmission of a ceftriaxone-resistant N gonorrhoeae strain that appears to have been circulating for more than 2 years, and that it's highly likely the strain is prevalent elsewhere but has yet to be detected. "These findings warrant the intensification of surveillance strategies and establishment of collaborations with other countries to monitor spread and inform national and global policies and actions," the authors write. See also: Mar 6 Lancet Infect Dis abstract Mar 6 Emerg Infect Dis paper |
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ECDC report on the above disease:
http://www.ecdc.europa.eu/en/publications-data/molecular-typing-neisseria-gonorrhoeae-study-2013-isolates Molecular typing of Neisseria gonorrhoeae – a study of 2013 isolatestechnical reportThis report describes the second molecular typing survey of N. gonorrhoeae across the European Union/European Economic Area (EU/EEA) and provides recent information on NG-MAST STs/Gs and genotypes based on whole genome sequencing (WGS) circulating in 21 EU/EEA Member States. This is the first time WGS has been used in any international surveillance programme for sexually transmitted infections. Executive summaryIn 2011, a pilot study was conducted to assess the public health value of molecular surveillance for gonorrhoea in 21 European Union/European Economic Area (EU/EEA) countries. A total of 1066 isolates collected as part of the 2010 European gonococcal antimicrobial surveillance programme (Euro-GASP) were typed using Neisseria gonorrhoeae Multi-Antigen Sequence typing (NG-MAST). The study highlighted many issues of importance for public health on national as well as EU/EEA level, including the identification of a highly heterogeneous gonococcal population with some predominant genogroups (Gs) and the establishment of a baseline for sequence types (STs) and Gs. The study showed that NG-MAST appeared to have a high discriminatory ability, provided enhanced surveillance data and improved the understanding of emergence and dissemination of gonococcal strains, including those with therapeutically relevant resistance profiles. Therefore NG-MAST (linked to antimicrobial resistance (AMR) profiles and epidemiological metadata) was considered useful for public health purposes at the EU/EEA level. The present study represents a new molecular epidemiological survey using Euro-GASP isolates from 2013 to further assess the spread of AMR gonococcal strains in the EU/EEA, to investigate the stability of the relationships between AMR and STs/Gs and to address additional issues of importance for public health. In addition, whole genome sequencing (WGS) was performed on all available isolates to establish if multidrug resistant STs/Gs are clonal and to detail their distribution, to assess the public health relevance of WGS in the surveillance and control of N. gonorrhoeae at EU/EEA level and to form an evidence base for a molecular surveillance strategy for N. gonorrhoeae in the EU/EEA. The 2013 study aimed to type 50 isolates from each country and 100
isolates from countries with higher rates of gonorrhoea by both NG-MAST
and WGS. A total of 1189 isolates were typed by NG-MAST; 430 (STs) were
identified, 146 of which were represented by two or more gonococcal
isolates. Twenty-three types were represented by ten or more isolates.
While considerable diversity was observed in different countries, four
STs (ST1407, ST2992, ST2400 and ST4995) were predominant, albeit at
different levels in individual countries. ST1407 and ST2992 also
predominated in 2010. However, in 2013, ST1407 represented only 7.6% of
all isolates, while in 2009-2010 it represented 15.6% of isolates. The
continuing predominance of a single NG-MAST ST is interesting given that
the gonococcus is highly heterogeneous and that NG-MAST measures
variation within two highly variable genes. Significant associations were identified between ciprofloxacin resistance and the predominant genogroups G1407, G2400, G225, G4995, G5624, G5333, and G7232. A strong association was identified between G1407 and resistance to cefixime and ciprofloxacin, with also a relatively large proportion (34%) of the G1407 isolates showing intermediate susceptibility or resistance to azithromycin. Similar associations were also found in the previous Euro-GASP molecular typing study. Consequently, G1407 genogroup continues to predominate even though cefixime is no longer recommended as the first-line therapeutic agent to treat gonorrhoea. Six G1407 isolates were also resistant to the first-line treatment ceftriaxone. Accordingly, the continued predominance of G1407 isolates in many EU/EEA Member States is worrying, given their potential to be therapeutically challenging. While G1407 was more associated with MSM in the Euro-GASP molecular typing study in 2009–2010 (despite being present in the heterosexual population), G1407 was associated with heterosexual patients as well as older patients (>45 years of age) in 2013 at a higher level. Thus, this multidrug-resistant genogroup appears to have crossed over to the heterosexual population in 2013. Obviously, the G1407 genogroup is circulating both in the heterosexual population as well as among MSM and, consequently, the potential risks of future treatment failure are not restricted to any one patient group. Quality assured WGS data linked to AMR profiles and epidemiological
data was obtained for 1054 (89%) isolates and the phylogenomics based on
the whole genome sequences revealed a significantly higher and more
accurate resolution of the isolates. WGS further discriminated isolates
with identical NG-MAST STs and Gs mostly reflecting specific
evolutionary traits in the same country. The WGS data revealed that
NG-MAST Gs (based on diversity in only two genes) do not always reflect
the genomic similarities or differences of isolates. Additionally, 114
different multilocus sequence typing (MLST) STs (40 new STs), including
68 clusters (≥2 isolates with identical ST) and 46 STs represented by
single isolates, were identified in silico from the WGS data. AMR
determinants, mainly all known resistance determinants for
sulphonamides, penicillins, tetracyclines, spectinomycin, rifampicin,
fluoroquinolones, macrolides (e.g. azithromycin), cefixime and
ceftriaxone were also identified in silico. The full PDF is available at: https://ecdc.europa.eu/sites/portal/files/documents/Molecular-typing-N-gonorrhoeae-web.pdf |
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