The gut mucosal immune system in the neonatal period.

Invasive sepsis in the newborn period is a major cause of childhood morbidity and mortality worldwide. The infant immune system undoubtedly differs intrinsically from the mature adult immune system. Current understanding is that the newborn infant immune system displays a range of competencies and is developing rather than deficient. The infant gut mucosal immune system is complex and displays a plethora of phenotypic and functional irregularities that may be clinically important. Various factors affect and modulate the infant gut mucosal immune system: components of the intestinal barrier, the infant gut microbiome, nutrition and the maternal-infant hybrid immune system. Elucidation of the phenotypic distribution of immune cells, their functional significance and the mucosa-specific pathways used by these cells is essential to the future of research in the field of infant immunology.

Susceptibility to invasive bacterial infections in children with sickle cell disease.

Individuals with sickle cell disease (SCD) demonstrate an increased susceptibility to invasive bacterial infections (IBI). The most common organisms causing IBI are Streptococcus pneumoniae, nontyphi Salmonella species and Haemophilus influenzae type b (Hib). IBI are the most common causes of death in children below 5 years of age with SCD. Increased susceptibility to IBI is because of several factors including dysfunctional antibody production and opsonophagocytosis as well as defective splenic clearance. Early diagnosis of Hib and pneumococcal infections combined with antibiotic prophylaxis and immunization programs, could lead to significant improvements in mortality, especially in Africa.

Antimicrobial Proteins and Peptides in Early Life: Ontogeny and Translational Opportunities.

While developing adaptive immune responses, young infants are especially vulnerable to serious infections, including sepsis, meningitis, and pneumonia. Antimicrobial proteins and peptides (APPs) are key effectors that function as broad-spectrum anti-infectives. This review seeks to summarize the clinically relevant functional qualities of APPs and the increasing clinical trial evidence for their use to combat serious infections in infancy. Levels of APPs are relatively low in early life, especially in infants born preterm or with low birth weight (LBW). There are several rationales for the potential clinical utility of APPs in the prevention and treatment of infections in infants: (a) APPs may be most helpful in those with reduced levels; (b) during sepsis microbial products signal via pattern recognition receptors causing potentially harmful inflammation that APPs may counteract; and (c) in the era of antibiotic resistance, development of new anti-infective strategies is essential. Evidence supports the potential clinical utility of exogenous APPs to reduce infection-related morbidity in infancy. Further studies should characterize the ontogeny of antimicrobial activity in mucosal and systemic compartments, and examine the efficacy of exogenous-APP formulations to inform translational development of APPs for infant groups.

Diagnosis, incidence, and outcomes of suspected typhlitis in oncology patients--experience in a tertiary pediatric surgical center in the United Kingdom.

BACKGROUND: Typhlitis is clinically defined by the triad of neutropenia, abdominal pain, and fever. Radiologic evidence of colonic inflammation supports the diagnosis. We report a single United Kingdom tertiary center experience with management and outcome of typhlitis for 5 years. METHODS: Hospital computerized records were screened for ultrasound or computerized tomographic scan requests for abdominal pain for all oncology inpatients (2001-2005). Retrospective case note analysis was used to collect clinical data for patients with features of typhlitis. RESULTS: The incidence of typhlitis among oncology inpatients was 6.7% (40/596) among oncology inpatients and 11.6% (40/345) among those on chemotherapy. Eighteen children had radiologically confirmed typhlitis, and 22 had clinical features alone. Most (93%) patients responded to conservative management. Eighteen children had a variable period of bowel rest, including 12 patients who were supported with total parenteral nutrition. Three patients had laparotomy that revealed extensive colonic bowel necrosis (1), perforated gastric ulcer (1), and a perforated appendix (1). A single child died of fulminant gram-negative sepsis without surgical intervention. CONCLUSIONS: The diagnosis of typhlitis was based on clinical features, supported by radiologic evidence in almost half of the study group. Surgical intervention should be reserved for specific complications or where another surgical pathologic condition cannot reasonably be ruled out.