Reduced Response to Multiple Vaccines Sharing Common Protein Epitopes That Are Administered Simultaneously to Infants

The plethora of newly discovered vaccines implies that, in the future, many vaccines will have to be administered simultaneously to infants. We examined the potential interference with the immune response of several coadministered vaccines containing the same protein component, namely, tetanus toxoid (TT). Infants simultaneously receiving a tetravalent pneumococcal vaccine conjugated to TT (PncT) and a diphtheria-tetanus-pertussis–poliovirus–Haemophilus influenzae type b-tetanus conjugate vaccine showed significantly lower anti-H. influenzae type b polysaccharide (polyribosylribitol phosphate [PRP]) antibody concentrations than those receiving either a tetravalent pneumococcal vaccine conjugated to diphtheria toxoid or placebo. A dose range study showed that anti-PRP antibody concentrations were inversely related to the TT content of the PncT vaccines administered in infancy. Postimmunization antitetanus antibody concentrations were also affected adversely as the TT content of the coadministered vaccines was increased. This phenomenon, which we believe derives from interference by a common protein carrier, should be taken into account when the introduction of an immunization program including multiple conjugate vaccines is considered.     

Clinical and bacterial characteristics of acute bacterial conjunctivitis in children in the antibiotic resistance era

BACKGROUND: Acute conjunctivitis is the most common eye disorder in young children. Bacteria are responsible for 54-73% of all cases. The goals of the study were to identify the rates of Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis in cases of bacterial conjunctivitis in children and to define antibiotic resistance rates. METHODS: During a 2-year study period, conjunctival swabs of children 2-36 months old were collected prospectively. Nontypable H. influenzae, S. pneumoniae and M. catarrhalis were defined as the study pathogens. Analyzed variables included demography, clinical presentation, bacteriologic results and susceptibility patterns. RESULTS: There were 428 patients enrolled. Of all cultures, 55% (237 of 428) yielded at least 1 of the study pathogens. H. influenzae and S. pneumoniae were isolated from 29 and 20% of cultures, respectively. beta-Lactamase production was found in 29% of H. influenzae isolates, and penicillin nonsusceptibility was observed in 60% of S. pneumoniae isolates. The most common S. pneumoniae serotypes were: 19F (14%); 6A and 14 (11% each). Nontypable S. pneumoniae was found in 12%. The 7-valent pneumococcal conjugate vaccine (PCV-7) could potentially cover 44% of all isolates. Conjunctivitis-otitis syndrome was found in 32% of patients, of whom 82% of cultures yielded H. influenzae. CONCLUSIONS: Antibiotic resistance rates are alarmingly high. Conjunctivitis-otitis syndrome, predominantly caused by H. influenzae, is quite common. The potential coverage of the PCV-7 in conjunctivitis is relatively lower than that reported in other pneumococcal infections. Our findings should alert physicians on the choice of appropriate antibiotic treatment, on the frequent copresence of acute otitis media and on the potential role of conjunctivitis in the spread of antibiotic-resistant pathogens.     

A prospective randomized,controlled trial of eculizumab to prevent ischemia‐reperfusion injury in pediatric kidney transplantation

Ischemia‐reperfusion injury has multiple effects on a transplanted allograft, including delayed or impaired graft function, compromised long‐term survival, and an association with an increased incidence of rejection. Eculizumab, a monoclonal antibody blocking terminal complement activation, has been postulated to be an effective agent in the prevention or amelioration of IRI. We performed a single‐center prospective, randomized controlled trial involving 57 pediatric kidney transplant recipients between 2012 and 2016. The immunosuppressive protocol included two doses of alemtuzumab; half of the patients were randomized to receive a single dose of eculizumab prior to transplantation. Maintenance immunosuppression was based on a combination of low‐dose tacrolimus and mycophenolate, without steroids. Eculizumab‐treated patients had a significantly better early graft function, less arteriolar hyalinosis and chronic glomerulopathy on a protocol biopsies taken on day 30, 1 year, and 3 years after transplantation. In the eculizumab group, four non‐vaccinated children lost their grafts during the course of a flu‐like infection. Eculizumab is associated with better early graft function and improved graft morphology; however, there was an unacceptably high number of early graft losses among the eculizumab‐treated children. While a promising strategy, the best approach to complement inhibition remains to be established.     

Epidemiology and outcome of chronic high Epstein‐Barr viral load carriage in pediatric kidney transplant recipients

The development of EBV infection and PTLD is normally associated with a high EBV viral load in peripheral blood. Observations have previously identified existence of a CHL carrier state that demonstrated variable outcomes based upon the organ which was transplanted. Data defining the incidence and outcome of CHL in pediatric KTx are not well described. The charts of children undergoing isolated KTx at Children's Hospital of Pittsburgh between January 2000 and December 2014 were retrospectively reviewed. EBV loads in the peripheral blood were routinely measured as part of surveillance protocols at our center. CHL was defined as the presence of high load for >50% of samples for ≥6 months. PTLD was defined histologically using WHO definitions. Of 188 isolated KTx recipients, we identified a total of 16 (8%) children who developed CHL carrier state. No patient developed EBV‐driven late‐onset PTLD. Age at the time of KTx was significantly lower in the CHL group (median 3.9 years, interquartile range: IQR 2.9‐6.6, P = .0004). Children in the CHL group were more likely to be EBV‐seronegative prior to KTx (94%, 15/16), compared to the UVL and LVL groups (55% and 50%, respectively, P < .002). The median duration of CHL carrier state was 20 months (IQR 10.7‐35.8). Fifteen of the 16 CHL carriers experienced spontaneous resolution of CHL carrier state. Children in the CHL group were younger at the time of primary EBV infection (P = .023). Finally, antiviral medication was not effective in either preventing or decreasing the EBV viral load in blood (P = .84). Overall incidence of late‐onset PTLD is very low compared to heart and intestinal transplant, even though KTx recipients can develop CHL carrier state. The CHL carriers in KTx recipients were EBV‐seronegative prior to transplant and were younger both at the time of KTx and at the time of primary EBV infection compared to those in the UVL and HVL groups. Antivirals did not prevent EBV infection or decrease EBV viral loads.     

Radiologic mimics of juvenile rheumatoid arthritis

Established criteria for diagnosis of juvenile rheumatoid arthritis require consideration of a number of other joint arthropathies and arthritides. In this pictorial essay, we present an approach to those common and uncommon disorders that should be considered and may be mistaken for juventile rheumatoid arthritis. Received: 22 May 2000 Accepted: 14 November 2000     

Maternal and fetal serum levels of organochlorine compounds in cases of premature rupture of membranes

Blood residue levels of some organochlorine pesticides (DDT and its analogues, lindane, dieldrin, heptachlor epoxide) and polychlorinated biphenyls were measured in maternal and cord blood in 20 cases of premature rupture of fetal membranes at term and in 15 matched controls. No evidence of a possible organochlorine compounds role in the pathogenesis of premature rupture of the membrane was found.