Co-circulation of Multidrug-resistant Shigella Among Men Who Have Sex With Men in Australia.

BACKGROUND: In urban Australia, the burden of shigellosis is either in returning travelers from shigellosis-endemic regions or in men who have sex with men (MSM). Here, we combine genomic data with comprehensive epidemiological data on sexual exposure and travel to describe the spread of multidrug-resistant Shigella lineages. METHODS: A population-level study of all cultured Shigella isolates in the state of Victoria, Australia, was undertaken from 1 January 2016 through 31 March 2018. Antimicrobial susceptibility testing, whole-genome sequencing, and bioinformatic analyses of 545 Shigella isolates were performed at the Microbiological Diagnostic Unit Public Health Laboratory. Risk factor data on travel and sexual exposure were collected through enhanced surveillance forms or by interviews. RESULTS: Rates of antimicrobial resistance were high, with 17.6% (95/541) and 50.6% (274/541) resistance to ciprofloxacin and azithromycin, respectively. There were strong associations between antimicrobial resistance, phylogeny, and epidemiology. Specifically, 2 major MSM-associated lineages were identified: a Shigellasonnei lineage (n = 159) and a Shigella flexneri 2a lineage (n = 105). Of concern, 147/159 (92.4%) of isolates within the S. sonnei MSM-associated lineage harbored mutations associated with reduced susceptibility to recommended oral antimicrobials: namely, azithromycin, trimethoprim-sulfamethoxazole, and ciprofloxacin. Long-read sequencing demonstrated global dissemination of multidrug-resistant plasmids across Shigella species and lineages, but predominantly associated with MSM isolates. CONCLUSIONS: Our contemporary data highlight the ongoing public health threat posed by resistant Shigella, both in Australia and globally. Urgent multidisciplinary public health measures are required to interrupt transmission and prevent infection

High serum cholesterol levels in persons with `high-normal' TSH levels: should one extend the definition of subclinical hypothyroidism?

Objective: The association between established hypothyroidism and high cholesterol levels is well known. The aim of the present study was to investigate the effect of thyroxine (T-4) administration on cholesterol levels in hypercholesterolemic subjects with TSH levels within the normal range (’high-normal’ TSH compared with ‘low-normal’ TSH). Design and Methods: We determined TSH levels in 110 consecutive patients referred for hypercholesterolemia (serum cholesterol > 7.5 mmol/l). Those with ‘high-normal’ TSH (2.0-4.0 mu U/ml) as well as those with ‘low-normal’ TSH (0.40-1.99 mu U/ml) were randomly assigned to receive either 25 or 50 mu g T-4 daily for two months. Thus, groups A and B (low-normal TSH) received 25 and 50 mu g T-4 respectively and groups C and D (high-normal TSH) received 25 and 50 mu g T-4 respectively. Serum T-4, tri-iodothyronine (T-3), TSH, free thyroxine index, resin T-3 uptake and thyroid autoantibodies (ThAab) as well as total cholesterol, high and low density lipoprotein cholesterol (HDL. LDL), and triglycerides were determined before and at the end of the two-month treatment period. Results: TSH levels were reduced in all groups, The most striking effect was observed in group D (TSH levels before: 2.77 +/- 0.55, after: 1.41 +/- 0.85 mu U/ml, P < 0.01). Subjects in groups C and D had a higher probability of having positive ThAabs. A significant reduction in total cholesterol (P < 0.01) and LDL (P < 0.01) was observed after treatment only in group D. In those subjects in group D who were ThAab negative, there was no significant effect of thyroxine on cholesterol levels. Conclusions: Subjects with high-normal TSH levels combined with ThAabs may, in fact, have subclinical hypothyroidism presenting with elevated cholesterol levels. It is possible that these patients might benefit from thyroxine administration