Implementation of type 1 diabetes genetic risk screening in children in diverse communities: the Virginia PrIMeD project.

BACKGROUND: Population screening for risk of type 1 diabetes (T1D) has been proposed to identify those with islet autoimmunity (presence of islet autoantibodies). As islet autoantibodies can be transient, screening with a genetic risk score has been proposed as an entry into autoantibody testing. METHODS: Children were recruited from eight general pediatric and specialty clinics across Virginia with diverse community settings. Recruiters in each clinic obtained informed consent/assent, a medical history, and a saliva sample for DNA extraction in children with and without a history of T1D. A custom genotyping panel was used to define T1D genetic risk based upon associated SNPs in European- and African-genetic ancestry. Subjects at "high genetic risk" were offered a separate blood collection for screening four islet autoantibodies. A follow-up contact (email, mail, and telephone) in one half of the participants determined interest and occurrence of subsequent T1D. RESULTS: A total of 3818 children aged 2-16 years were recruited, with 14.2% (n = 542) having a "high genetic risk." Of children with "high genetic risk" and without pre-existing T1D (n = 494), 7.0% (34/494) consented for autoantibody screening; 82.4% (28/34) who consented also completed the blood collection, and 7.1% (2/28) of them tested positive for multiple autoantibodies. Among children with pre-existing T1D (n = 91), 52% (n = 48) had a "high genetic risk." In the sample of children with existing T1D, there was no relationship between genetic risk and age at T1D onset. A major factor in obtaining islet autoantibody testing was concern over SARS-CoV-2 exposure. CONCLUSIONS: Minimally invasive saliva sampling implemented using a genetic risk score can identify children at genetic risk of T1D. Consent for autoantibody screening, however, was limited largely due to the SARS-CoV-2 pandemic and need for blood collection.

Characterization of a Staphylococcus aureus USA300 protein signature using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Staphylococcus aureus strain type USA300 is an important human pathogen. Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry has been used successfully for rapid identification of S. aureus at the genus and species levels. Here, it was hypothesized that MALDI-TOF could be used to identify USA300 organisms at the strain level. A genetic algorithm model using ClinProTools software (Bruker Daltonics) was built using 47 isolates of USA300 S. aureus and 77 non-USA300 S. aureus isolates. Three mass/charge peaks (5932, 6423 and 6592) were found to be discriminators between the groups of isolates. The model was validated using 224 test isolates: 197 of 224 test isolates were correctly classified as 'USA300 family' or 'non-USA300'. The sensitivity of the model was 0.87, with a specificity of 0.89, positive likelihood ratio of 8.19 and negative likelihood ratio of 0.15. The three-peak intensity MALDI-TOF model designed and tested in the current study can be used to rapidly identify USA300 family S. aureus isolates with reasonable sensitivity and specificity.

Ceftriaxone-induced hemolysis in a child with Lyme arthritis: a case for antimicrobial stewardship.

Guidelines for the treatment of Lyme arthritis were published by the Infectious Diseases Society of America in 2006 and recommended oral doxycycline for initial therapy. We report here the case of a young girl treated with intravenous ceftriaxone who subsequently developed drug-induced autoimmune hemolytic anemia and renal failure. Her severe sequelae highlight the importance of antimicrobial stewardship. We review here the goals of antimicrobial stewardship and several strategies for achieving them. In addition, we briefly discuss the rare adverse drug event experienced by our patient.

Pathogen identification using mass spectrometry in the clinical microbiology laboratory.

The recent application of Matrix-assisted Laser Desorption/Ionization Time-of-Flight and Polymerase Chain Reaction Electrospray Ionization Quadrupole Time-of-Flight mass spectrometry approaches to microbial identification has initiated a revolution in the clinical microbiology lab. The commercial application of these technologies to pathogen identification has only begun in the last five years, and already new potentially life-saving applications of these technologies are rapidly identifying organisms that in the past have proven notoriously difficult to identify. In this review, we will provide a brief historical perspective on how these developments arose, describe why they are being successfully applied now and provide an overview of current approaches. Using examples involving clinical isolates of Staphylococcus aureus, a perspective on future use and developments of mass spectrometry in the identification of microbial organisms is provided.