Humoral and cell-mediated immune responses to monovalent 2009 influenza A/H1N1 and seasonal trivalent influenza vaccines in high-risk children.

OBJECTIVE: Humoral and cell-mediated immune responses to monovalent 2009 pandemic influenza A (H1N1/2009) and seasonal trivalent influenza (TIV) vaccines were evaluated in healthy children and children with asthma, sickle cell disease (SCD), systemic lupus erythematosus (SLE), and solid organ transplantation (SOT). STUDY DESIGN: Blood was collected from 112 subjects at the time of H1N1/2009 vaccination and 46 ± 15 days later for hemagglutination inhibition titers and γ-interferon ELISPOT responses to H1N1/2009 vaccine and TIV; unvaccinated children also received TIV at enrollment. RESULTS: A significant increase in the percentage of subjects with seroprotective hemagglutination inhibition titers to both vaccines was observed in all high-risk groups. Children with asthma and SCD were most likely to achieve seroprotective titers to H1N1/2009, whereas <50% of subjects with SOT and SLE had a seroprotective response. Subjects with SOT and SLE also had lower rates of seroprotection after TIV, and subjects with SLE had the lowest ELISPOT responses to both vaccines. Overall, 73% of healthy children exhibited protective responses to TIV; only 35% achieved seroprotection for H1N1/2009. CONCLUSIONS: This evaluation of immune responses to H1N1/2009 in high-risk children suggests suboptimal responses for SOT and SLE subjects, but not for subjects with SCD or asthma. Higher antigen dose, additional dose regimens, or both for immunocompromised children warrant further investigation.

Dynamics of cell-mediated immune responses to cytomegalovirus in pediatric transplantation recipients.

CMI responses, combined with quantification of CMV DNA (DNAemia), may identify transplantation recipients at risk for invasive disease. PBMC were collected in pediatric transplantation candidates at one, three, and six months post-transplant in 10 subjects (six renal, three cardiac, one stem cell) and at single time points in eight HC and 14 children greater than one yr post-transplant (LTTx). Cells were stimulated with anti-CD3mAb or CMV pp65 peptide pools and responses assessed by IFNG enzyme-linked immunosorbent spot assay and cytokine secretion. IFNG responses to anti-CD3mAb were significantly lower pretransplant relative to HC and were further decreased at one and three months post-transplant, but recovered to levels comparable to HC by six months. Responses to pp65 among CMV-seropositive recipients followed a similar pattern but recovered by three months. CMV-seropositive LTTx and HC showed a Th1 cytokine response to pp65 stimulation. Three LTTx subjects developed CMV DNAemia; two demonstrated decreased responses to anti-CD3mAB (and pp65 in the CMV seropositive subject) at the onset of DNAemia, which recovered as DNAemia resolved. Monitoring CMI in children is feasible and may provide an adjunct biomarker to predict CMV progression and recovery.

Postoperative mediastinitis in children: epidemiology, microbiology and risk factors for Gram-negative pathogens.

BACKGROUND: Mediastinitis, although an infrequent complication of median sternotomy, represents a significant source of morbidity and mortality. OBJECTIVE: To determine the incidence and describe the epidemiology and microbiology of mediastinitis in children after cardiac surgery and to identify risk factors for the development of Gram-negative mediastinitis. STUDY DESIGN: This was a retrospective case-control study nested within the cohort of children, birth to 18 years of age, undergoing median sternotomy between January 1, 1995 and December 31, 2003. RESULTS: Forty-three cases of mediastinitis were identified. The incidence of mediastinitis was 1.4%. Median patient age at time of inciting sternotomy was 32 days (interquartile range, 5 days-9 months). Twenty-three (54%) cases occurred in girls. Median time to onset of infection after surgery was 11 days (range, 4-34 days). Overall Gram-positive organisms were present in 29 (67%) cases, and Gram-negative organisms were present in 13 (30%) cases. The organisms most commonly isolated from mediastinal culture were Staphylococcus aureus (46%), coagulase-negative staphylococci (17%) and Pseudomonas aeruginosa (17%). The rate of concurrent bacteremia was 53% (95% confidence interval, 38-69%). In multivariable analysis, delayed sternal closure was an independent risk factor for the development of Gram-negative mediastinitis (odds ratio, 9.3; 95% confidence interval, 1.5-56.8; P = 0.016). CONCLUSIONS: Although Gram-positive organisms were the most common cause of infection, Gram-negative organisms accounted for one-third of all isolates. More than one-half of patients with mediastinitis had concurrent bacteremia. Delayed sternal closure was an independent risk factor for Gram-negative mediastinitis.

Staphylococcus aureus as a risk factor for bloodstream infection in children with postoperative mediastinitis.

Bloodstream infection (BSI) complicates postoperative mediastinitis in >50% of cases. In this retrospective cohort study from 1995-2003, postoperative mediastinitis caused by Staphylococcus aureus was an independent risk factor for the development of BSI (adjusted odds ratio, 6.4; 95% confidence interval, 1.4-29.3). Postoperative mediastinitis caused by S. aureus has a higher intrinsic risk of being complicated by BSI than mediastinitis caused by other pathogens.

Diagnosis and management of community-associated MRSA infections in children.

The history of antibiotic resistance in Staphylococcus aureus spans more than half a century. Methicillin-resistant S. aureus (MRSA) has emerged as an almost ubiquitous pathogen in both the community and hospital settings. The predominant clone responsible for community-associated MRSA, USA300, is a highly successful pathogen, as demonstrated by its rapid global spread and associated morbidity and mortality. The management of MRSA infections in pediatric patients is complicated by the limited number of effective antibiotics that have been well-studied in children. The gold standard antimicrobial, vancomycin, has several shortcomings that have prompted the development of newer agents for the treatment of MRSA disease. Moreover, the emergence of vancomycin-intermediate or -resistant S. aureus, while uncommon, portends a potential new era of resistance that will require research and development of the next generation of antibiotics that act by novel mechanisms.