Bacterial Genotype, Carrier Risk Factors, and an Antimicrobial Stewardship Approach Relevant to Methicillin-resistant Staphylococcus aureus Prevalence in a Population of Macaques Housed in a Research Facility.

Methicillin-resistant Staphylococcus aureus (MRSA) remains a significant problem for human and animal health and can negatively affect the health status of macaques and other nonhuman primates (NHP) in research colonies. However, few publications provide guidance on the prevalence, genotype, or risk factors for macaques with MRSA and even fewer on how to effectively respond to MRSA once identified in a population. After having a clinical case of MRSA in a rhesus macaque, we sought to determine the MRSA carrier prevalence, risk factors, and genotypes of MRSA in a population of research NHPs. Over a 6-wk period in 2015, we collected nasal swabs from 298 NHPs. MRSA was isolated from 28% (n = 83). We then reviewed each macaque's medical record for a variety of variables including animal housing room, sex, age, number of antibiotic courses, number of surgical interventions, and SIV status. Analysis of these data suggests that MRSA carriage is associated with the room location, age of the animal, SIV status, and the number of antibiotic courses. We used multilocus sequence typing and spa typing on a subset of MRSA and MSSA isolates to determine whether the MRSA present in NHPs was comparable with common human strains. Two MRSA sequence types were predominant: ST188 and a novel MRSA genotype, neither of which is a common human isolate in the United States. We subsequently implemented antimicrobial stewardship practices (significantly reducing antimicrobial use) and then resampled the colony in 2018 and found that MRSA carriage had fallen to 9% (26/285). These data suggest that, as in humans, macaques may have a high carrier status of MRSA despite low clinically apparent disease. Implementing strategic antimicrobial stewardship practices resulted in a marked reduction in MRSA carriage in the NHP colony, highlighting the importance of limiting antimicrobial use when possible.

Factors Influencing Implementation of Evidence-Based Mental Health Interventions for Infants and Young Children.

Large-scale efforts have been made to adopt evidence-based practices (EBPs) for young children within community mental health settings. The current study investigated the implementation of Parent-Child Interaction Therapy and Child-Parent Psychotherapy using an online survey of 20 program managers representing 16 birth-to-five mental health agencies serving an ethnically diverse Medicaid population throughout a large urban county. Survey questions addressed intake and referral processes, training and supervision in EBPs, treatment fidelity, and patient outcomes/satisfaction. Results indicated that both clinical judgment and established decision-trees were used to select treatment approaches and that supervision, consultation, and fidelity monitoring were used to support fidelity to the models. Participants cited intensive EBP training processes, staff turnover, and patient attrition as barriers to sustainability. Implications regarding implementation of EBPs for infants and young children are discussed, including issues related to patient care, training and supervision, treatment fidelity, program sustainability, and barriers to system change.

T-cell responses to KSHV infection: a systematic approach.

Prior studies of T-cell responses to KSHV have included relatively few participants and focused on relatively few KSHV antigens. To provide a more comprehensive analysis, we investigated T-cell responses to the whole KSHV proteome using IFN-γ ELISpot. Using ∼7,500 overlapping 15mer peptides we generated one to three peptide pools for each of the 82 KSHV ORFs. IFN-γ ELISpot analysis of PBMCs from 19 patients with a history of KSHV-associated disease and 24 healthy donors (11 KSHV seropositive) detected widely varied responses. Fifty six of the 82 ORFs were recognized by at least one individual but there was little overlap between participants. Responses to at least one ORF pool were observed in all 19 patients and in 7 seropositive donors. Four seropositive donors and 10 seronegative donors had no detectable responses while 3 seronegative donors had weak responses to one ORF. Patients recognised more ORFs than the donors (p=0.04) but the response intensity (spot forming units: SFU per million cells) was similar in the two groups. In four of the responding donors, individual peptides eliciting the predominant responses were identified: three donors responded to only one peptide per ORF, while one recognized five. Using intracellular cytokine staining in four participant samples, we detected peptide-induced IFN-γ, MIP1-ß, and TNF-α as well as CD107a degranulation, consistent with multifunctional effector responses in CD8+ and CD4+ T cells. Sequence analysis of TCRs present in peptide specific T-cell clones generated from two participants showed both mono- and multi-clonotypic responses. Finally, we molecularly cloned the KSHV specific TCRs and incorporated the sequences into retroviral vectors to transfer the specificities to fresh donor cells for additional studies. This study suggests that KSHV infected individuals respond to diverse KSHV antigens, consistent with a lack of shared immunodominance and establishes useful tools to facilitate KSHV immunology studies.