No abstract

Here we present a case series from a primate research facility. The index case, a 4-year-old pig-tailed macaque (Macaca nemestrina) experimentally infected with chimeric simian-human immunodeficiency virus (SHIVSF162 P4), developed weight loss and was euthanized. Based on necropsy results the animal was diagnosed with opportunistic atypical mycobacteriosis associated with simian AIDS (SAIDS). Subsequently, tissues from the index animal, as well as tissues and oral mucosal swabs from six SHIV-infected contacts, were analyzed using molecular methods and found to contain nucleic acid sequences characteristic of Mycobacterium tuberculosis complex (MTBC). These data suggest that existing protocols fail to reliably detect MTBC infection in laboratory primates used as experimental models.

BACKGROUND Following trauma, persistent inflammation, immunosuppression, and catabolism may characterize delayed recovery or failure to recover. Understanding the metabolic response associated with these adverse outcomes may facilitate earlier identification and intervention. We characterized the metabolic profiles of trauma victims who died or developed chronic critical illness (CCI) and hypothesized that differences would be evident within 1-week postinjury. METHODS Venous blood samples from trauma victims with shock who survived at least 7 days were analyzed using mass spectrometry. Subjects who died or developed CCI (intensive care unit length of stay of ≥14 days with persistent organ dysfunction) were compared with subjects who recovered rapidly (intensive care unit length of stay, ≤7 days) and uninjured controls. We used partial least squares discriminant analysis, t tests, linear mixed effects regression, and pathway enrichment analyses to make broad comparisons and identify differences in metabolite concentrations and pathways. RESULTS We identified 27 patients who died or developed CCI and 33 who recovered rapidly. Subjects were predominantly male (65%) with a median age of 53 years and Injury Severity Score of 36. Healthy controls (n = 48) had similar age and sex distributions. Overall, from the 163 metabolites detected in the samples, 56 metabolites and 21 pathways differed between injury outcome groups, and partial least squares discriminant analysis models distinguished injury outcome groups as early as 1-day postinjury. Differences were observed in tryptophan, phenylalanine, and tyrosine metabolism; metabolites associated with oxidative stress via methionine metabolism; inflammatory mediators including kynurenine, arachidonate, and glucuronic acid; and products of the gut microbiome including indole-3-propionate. CONCLUSIONS The metabolic profiles in subjects who ultimately die or develop CCI differ from those who have recovered. In particular, we have identified differences in markers of inflammation, oxidative stress, amino acid metabolism, and alterations in the gut microbiome. Targeted metabolomics has the potential to identify important metabolic changes postinjury to improve early diagnosis and targeted intervention. LEVEL OF EVIDENCE Prognostic/epidemiologic, level III.