Zoonotic transmission of diphtheria toxin-producing Corynebacterium ulcerans.

BACKGROUND: Diphtheria caused by toxin-producing Corynebacterium ulcerans is a re-emerging human disease that can cause local and systemic sequelae. In Australia, toxigenic diphtheria is a rare notifiable communicable disease, due to high-vaccination coverage. The public health management of cutaneous cases of toxigenic C. ulcerans varies between jurisdictions, as opposed to the more uniform public health response to toxigenic Corynebacterium diphtheriae presenting as respiratory or laryngeal diphtheria. AIM: To report a case of zoonotically acquired C. ulcerans, review evidence on the zoonotic reservoir and reported transmission events, and examine public health guidelines for the management of human and animal contacts. METHODS AND RESULTS: In this case report, we detail our case investigation, treatment and public health management, including contact tracing and an approach to animal testing. We successfully identified companion canines as probable sources for the human case, with WGS confirming the link. The zoonotic disease link of C. ulcerans to domestic and agricultural animals is established in the literature; however, the management of animal contacts in human cases is inconsistent with jurisdictional or national guidelines. CONCLUSIONS: While a rare disease, a consistent approach to public health management is warranted to systematically elucidate the disease source and improve understanding of transmission.

Mycoplasma and Ureaplasma Donor-Derived Infection and Hyperammonemia Syndrome in 4 Solid Organ Transplant Recipients From a Single Donor.

Hyperammonemia syndrome (HS) is a life-threatening condition occurring in solid organ transplant patients, affecting primarily lung recipients, and is associated with Mycoplasma hominis and/or Ureaplasma spp infection. The organ donor was a young man who died of hypoxic brain injury and had urethral discharge antemortem. The donor and 4 solid organ transplant recipients had infection with M hominis and/or Ureaplasma spp. The lung and heart recipients both developed altered conscious state and HS associated with M hominis and Ureaplasma spp infections. Despite treatment with antibiotics and ammonia scavengers, both the lung and heart recipients died at day +102 and day +254, respectively. After diagnosis in the thoracic recipients, screening samples from the liver recipient and 1 kidney recipient were culture positive for M hominis with or without Ureaplasma spp. Neither the liver nor kidney recipients developed HS. Our case series demonstrates the unique finding of M hominis and Ureaplasma spp dissemination from an immunocompetent donor across 4 different organ recipients. Phylogenetic whole genome sequencing analysis demonstrated that M hominis samples from recipients and donor were closely related, suggesting donor-derived infection. Screening of lung donors and/or recipients for Mycoplasma and Ureaplasma spp is recommended, as well as prompt treatment with antimicrobials to prevent morbidity.

Field trials of blood culture identification FilmArray in regional Australian hospitals.

Purpose. In this field trial of rapid blood culture identification (BCID), we aimed to determine whether the improved speed and accuracy of specific BCID predicted in our earlier pilot study could be obtained in regional hospitals by deploying a multiplex PCR FilmArray (Biomerieux, France) capability in their laboratories.Methods. We trained local hospital laboratory staff to operate the FilmArray equipment and act on the results. To do this, we integrated the multiplex PCR into the standard laboratory blood culture workflow and reporting procedure.Results. Of 100 positive blood culture episodes, BCID FilmArray results were correct in all 42 significant monobacterial cultures, with a fully predictive identity in 38 (90.5 %) and a partial identity in another four (9.5 %). There was one major error; a false positive Pseudomonas aeruginosa. The minor errors were the detection of one methicillin-resistant Staphylococcus aureus, which proved to be a methicillin-sensitive S. aureus mixed with a methicillin-resistant coagulase-negative staphylococcus, five false negative coagulase-negative staphylococci and one false negative streptococcus species. We found that 41/49 (84 %) clinically significant mono- and polymicrobial culture results were fully predictive of culture-based identification to bacterial species level at a mean of 1.15 days after specimen collection.Conclusions. There was a reduction of 1.21 days in the time taken to produce a definitive BCID compared to the previous year, translating into earlier communication of more specific blood culture results to the treating physician. Reduced time to definitive blood culture results has a direct benefit for isolated Australian communities at great distances from specialist hospital services.

CDC73/HRPT2 CpG island hypermethylation and mutation of 5'-untranslated sequence are uncommon mechanisms of silencing parafibromin in parathyroid tumors.

The tumor suppressor HRPT2/CDC73 is mutated in constitutive DNA from patients with the familial disorder hyperparathyroidism-jaw tumor syndrome and in approximately 70% of all parathyroid carcinomas. In a number of HRPT2 mutant tumors however, expression of the encoded protein parafibromin is lost in the absence of a clear second event such as HRPT2 allelic loss or the presence of a second mutation in this tumor suppressor gene. We sought to determine whether hypermethylation of a 713 bp CpG island extending 648 nucleotides upstream of the HRPT2 translational start site and 65 nucleotides into exon 1 might be a mechanism contributing to the loss of expression of parafibromin in parathyroid tumors. Furthermore, we asked whether mutations might be present in the 5'-untranslated region (5'-UTR) of HRPT2. We investigated a pool of tissue from 3 normal parathyroid glands, as well as 15 individual parathyroid tumor samples including 6 tumors with known HRPT2 mutations, for hypermethylation of the HRPT2 CpG island. Methylation was not identified in any specimens despite complete loss of parafibromin expression in two parathyroid carcinomas with a single detectable HRPT2 mutation and retention of the wild-type HRPT2 allele. Furthermore, no mutations of a likely pathogenic nature were identified in the 5'-UTR of HRPT2. These data strongly suggest that alternative mechanisms such as mutation in HRPT2 intronic regions, additional epigenetic regulation such as histone modifications, or other regulatory inactivation mechanisms such as targeting by microRNAs may play a role in the loss of parafibromin expression.