Host Immune Transcriptional Profiles Reflect the Variability in Clinical Disease Manifestations in Patients with Staphylococcus aureus Infections

Staphylococcus aureus infections are associated with diverse clinical manifestations leading to significant morbidity and mortality. To define the role of the host response in the clinical manifestations of the disease, we characterized whole blood transcriptional profiles of children hospitalized with community-acquired S. aureus infection and phenotyped the bacterial strains isolated. The overall transcriptional response to S. aureus infection was characterized by over-expression of innate immunity and hematopoiesis related genes and under-expression of genes related to adaptive immunity. We assessed individual profiles using modular fingerprints combined with the molecular distance to health (MDTH), a numerical score of transcriptional perturbation as compared to healthy controls. We observed significant heterogeneity in the host signatures and MDTH, as they were influenced by the type of clinical presentation, the extent of bacterial dissemination, and time of blood sampling in the course of the infection, but not by the bacterial isolate. System analysis approaches provide a new understanding of disease pathogenesis and the relation/interaction between host response and clinical disease manifestations

A Case of Idiopathic Hypereosinophilic Syndrome Causing Mitral Valve Papillary Muscle Rupture

Idiopathic Hypereosinophilic Syndrome (IHES) is a rare disease that can be difficult to diagnose as the differential is broad. This disease can cause significant morbidity and mortality if left untreated. Our patient is a 17-year-old adolescent female who presented with nonspecific symptoms of abdominal pain and malaise. She was incidentally found to have hypereosinophilia of 16,000 on complete blood count and nonspecific colitis and pulmonary edema on computed tomography. She went into cardiogenic shock due to papillary rupture of her mitral valve requiring extreme life support measures including intubation and extracorporal membrane oxygenation (ECMO) as well as mitral valve replacement. Pathology of the valve showed eosinophilic infiltration as the underlying etiology. The patient was diagnosed with IHES after the exclusion of infectious, rheumatologic, and oncologic causes. She was treated with steroids with improvement of her symptoms and scheduled for close follow-up. In general patients with IHES that have cardiac involvement have poorer prognoses

Viral Bacterial Interactions in Children: Impact on Clinical Outcomes.

Respiratory viral infections are associated with significant morbidity and mortality in childre

Culture Negative Stent Infection in an Infant with Hypoplastic Left Heart and Persistent Fever

We present an infant with hypoplastic left heart with persistent fever despite two courses of antibiotics and repeatedly negative blood cultures. He eventually underwent surgical extraction of two stents. The stent cultures became positive; he was treated with 4 weeks of antibiotics and the fever resolved

PREVALENCE AND RISK FACTORS ASSOCIATED WITH THE PRRS VIRUS IN SEMEN OF BOARS IN PIG FARMS OF YUCATAN

The objectives of the present study were to estimate the prevalence of and to determine the risk factors associated with the porcine reproductive and respiratory syndrome virus (PRRSV, American strain) in semen of boars in pig herds of Yucatan, Mexico. Ninety two boars from 26 herds were ejaculated once. Semen samples were processed by the RT-nPCR test using the ORF7 primer to detect the PRRS virus. The true prevalence estimated was 10.1% (95% CI = 4.1-16.1%). Significance of risk factors was determined by Fisher-exact test. The odds of detecting genetic material of the PRRSV was greater (OR = 9.2) in semen of boars used under natural mating than those used in artificial insemination. In herds where boar’s acclimatization was not practiced the odds of a positive boar was 4.3. Another risk factor (P < 0.05) was the origin of the animals. In conclusion, the prevalence of the PRRSV in boar semen was smaller to the notified in the literature and determinate in blood serum. Management practices, such as the use of the artificial insemination and acclimatization of the boar, could be useful in reducing the prevalence of the PRRS virus in the pig farms

Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease.

BACKGROUND:Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. METHODS:Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4-6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. RESULTS:We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. CONCLUSION:A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG