Tatsuru Yamanaka

Gelatin-specific humoral and cellular immune responses in children with immediate- and nonimmediate-type reactions to live measles, mumps, rubella, and varicella vaccines ☆ ☆☆ ★

BACKGROUND This study was designed to investigate the development of both cellular and humoral immune responses to gelatin in patients with vaccine-related immediate and nonimmediate reactions. Our purpose was to define the nature of the responses in the different clinical states. METHODS Six patients with immediate reactions and 21 patients with nonimmediate reactions after inoculation of various live vaccines were studied. Measurement of gelatin-specific IgE was performed in all subjects. Gelatin-specific T-cell responses detected by an in vitro lymphocyte proliferation assay and by an assay for IL-2 responsiveness were investigated to compare the immune response in patients with the two types of reaction. RESULTS All six patients with immediate reactions had IgE responses to gelatin, whereas none of the 21 patients with nonimmediate reactions had any anti-gelatin IgE. All of the six patients with immediate reactions and 17 of the 21 patients with nonimmediate reactions exhibited positive T-lymphocyte responses specific to gelatin. CONCLUSIONS Immediate and nonimmediate reactions are caused by different types of allergy to gelatin, and cell-mediated immunity to gelatin may play an important role in the pathogenesis of nonimmediate reactions.

Single genotype of measles virus is dominant whereas several genotypes of mumps virus are co-circulating.

We have reported that in Japan measles virus strains have been classified into three distinct different genotypes (C1, D3 and D5) under the new international genotype classification since 1984. Similarly, mumps virus strains have been divided into two genotypes with three subtypes (B1, B2, B3, and D) under the proposed international classification since 1976. To differentiate these genotypes we developed a restriction fragment length polymorphism assay in the hemagglutinin (H) region for measles virus and in the hemagglutinin‐neuraminidase (HN) region for mumps virus to facilitate the expanded molecular epidemiology. In the Sapporo 1995/1996 measles outbreak, all 26 strains were classified as D5. Among 32 samples from patients with measles from 1994 to 1997 in Tokyo, 28 were identified as D5 and four were D3; these D3 strains were ascertained as a same hospital acquired infection. Among 45 strains obtained in the Tokyo 1999 outbreak, 38 were D3 and the remaining seven were D5. The dominant genotype of measles in Tokyo has replaced from D5 to D3 similar to the Chicago1/89 strain. We obtained 220 samples from patients with mumps from 1993 to 1997 and they were classified into one strain of B1, 14 strains of B2, 151 strains of B3, and 54 strains of D. Therefore, we suggest that two or three subtypes of mumps virus are co‐circulating with a different geographic pattern in genotype distribution, whereas a single measles virus genotype is dominantly observed, showing different epidemiological patterns. J. Med. Virol. 62:278–285, 2000.

A strong association between HLA-DR9 and gelatin allergy in the Japanese population

The frequency of HLA class I and II phenotypes was determined among 23 patients with positive gelatin IgE, eight of whom developed anaphylaxis, 18 patients who did not have gelatin IgE but who experienced non-immediate reactions after exposure to gelatin. HLA-DR9, which is unique to Orientals, was present in 56.5% of the gelatin IgE positive patients, as compared to control population frequency of 24% (P < 0.002). In the non-immediate reaction group, who did not generate IgE, phenotype distribution resembled controls. HLA-DR9 positive individuals have a relative risk of 4.1 for developing gelatin allergy with positive IgE.

The relevance of TH1 and TH2 cells in immediate and nonimmediate reactions to gelatin-containing vaccine.

BACKGROUND The immune mechanism of gelatin allergy, especially the participation of TH1 and TH2 cells and their cytokine secretion, has not been investigated. OBJECTIVE We investigated the characteristics of T lymphocytes from patients allergic to gelatin-containing vaccine by secondary in vitro stimulation of circulating mononuclear cells with gelatin. METHODS We studied 8 children with a history of immediate-type reactions and 8 with nonimmediate-type reactions after inoculation of gelatin-containing vaccine. The expression of IFN-gamma (TH1 ), IL-2 (TH1 ), IL-4 (TH2 ), and IL-13 (TH2 ) mRNA was examined semiquantitatively by using a reverse transcriptase PCR. IgE antibody to bovine gelatin was measured with the fluorometric ELISA system, and gelatin-specific T-cell responses were detected by an in vitro lymphocyte proliferation assay. RESULTS Patients with an immediate reaction all had gelatin-specific IgE antibody, whereas others did not. However, all patients exhibited positive T-lymphocyte responses specific to gelatin. Lymphocytes from subjects with nonimmediate-type reactions generally expressed very weak or sometimes no IFN-gamma, IL-2, or IL-13 genes and especially no IL-4 gene. On the other hand, the lymphocytes of subjects with immediate-type reactions significantly expressed not only IL-4 and IL-13 but also IFN-gamma and IL-2 mRNA. CONCLUSION Our observations suggest that both gelatin-specific TH2 and TH1 responses are involved in the pathogenesis of the immediate reaction to gelatin. The gelatin-specific IL-4 and/or IL-13 responses consistently observed in patients with an immediate reaction may be associated with the production of gelatin-specific IgE antibody.

Predominant Dissemination of PVL-Negative CC89 MRSA with SCCmec Type II in Children with Impetigo in Japan

Background. The ratio of CA-MRSA in children with impetigo has been increasing in Japan. Methods. Antimicrobial susceptibilities of 136 S. aureus isolates from children with impetigo were studied. Furthermore, molecular epidemiological analysis and virulence gene analysis were performed. Results. Of the 136 S. aureus isolates, 122 (89.7%) were MSSA and 14 (10.3%) were MRSA. Of the 14 MRSA strains, 11 belonged to CC89 (ST89, ST91, and ST2117) and carried diverse types of SCCmec: type II (IIb: 3 strains; unknown subtype: 4 strains), type IVa (2 strains), and unknown type (2 strains). The remaining three strains exhibited CC8 (ST-8)-SCCmec type VIa, CC121 (ST121)-SCCmec type V, and CC5 (ST5)-nontypeable SCCmec element, respectively. None were lukS-PV-lukF-PV gene positive. Gentamicin- and clarithromycin-resistant strains were frequently found in both MRSA and MSSA. Conclusions. PVL-negative CC89-SCCmec type II strains are the most predominant strains among the CA-MRSA strains circulating in the community in Japan.

Specific IgG to gelatin in children with systemic immediate-and nonimmediate-type reactions to measles, mumps and rubella vaccines

We examined anti-gelatin IgG in sera of children who suffered from systemic adverse reactions upon immunization with gelatin-containing live virus vaccines. In the group of 30 children who had immediate-type reactions and anti-gelatin IgE, 30 (100%) had anti-gelatin IgG and 29 (96%) had anti-gelatin IgG4. In another group of 75 children who had nonimmediate-type reactions and no anti-gelatin IgE, 22 (29%) had anti-gelatin IgG and six (8%) had IgG4. The IgG positivity well correlated with the lymphocyte proliferation assay positivity. In contrast, as a negative control, all 24 children who had no allergic reaction to live virus vaccines had no anti-gelatin IgG and IgG4. The results suggest that immune-response to gelatin may play a role in the pathogenesis of systemic nonimmediate-type reactions to the live virus vaccines.

Clinical Effect and Metabolism of S‐Sulfonated Immunoglobulin in 7 Patients with Congenital Humoral Immunodeficiency

Abstract. 7 patients with primary humoral immunodeficiency were given an S‐sulfonated IgG preparation, 100 mg/kg i.v. at intervals of 3–4 weeks, for treatment of, or prophylaxis against, infection. The clinical effects and metabolism of S‐sulfonated IgG were studied. No side reactions attributable to S‐sulfonated IgG occurred in any of the patients. The S‐sulfonated IgG was completely transformed into intact IgG within 24 h after administration, and had a mean half‐life of 21 days, comparable to that of intact IgG. Complete restoration of IgG Fc fragment activity occurred within 24 h following injection, as assessed by reversed passive cutaneous anaphylaxis.

Therapeutic effect of clarithromycin for respiratory-tract infections in children caused by Chlamydia pneumoniae

Children infected with Chlamydia pneumoniae sometimes experience lower respiratory tract infections such as pneumonia and bronchitis. Although numerous anti-microbial compounds have been reported to be active against the organism, most of them have not been in a clinical trial in infants and children with C. pneumoniae infection. Clarithromycin has been shown to express anti-chlamydial effects in vitro. In this study, we evaluated the clinical anti-C. pneumoniae properties of clarithromycin in children with mainly lower respiratory tract infection. We administered clarithromycin orally to 21 infants and children at a dose of 10-15 mg/kg/day divided into two or three doses for 4-21 days. Clinical symptoms, roentgenographic and laboratory abnormal findings improved. The overall clinical efficacy rate was 85.7% (18 of 21 cases). Administration of clarithromycin was considered to be a suitable treatment for improving lower respiratory infections in infants and children caused by C. pneumoniae.

Efficacy of antibiotic prophylaxis for intrafamilial transmission of group A beta-hemolytic streptococci.

Background: The role of chemoprophylaxis for household contacts of patients with acute streptococcal disease is uncertain. Methods: The subjects were 1440 sibling contacts of 1181 index patients with group A β-hemolytic streptococcal (GABHS) pharyngitis. Instances of subsequent GABHS pharyngitis in sibling contacts who received chemoprophylaxis and in a control group without prophylaxis were compared. Results: Of the 948 siblings in the prophylaxis group, 507 were treated with cephalosporins and 441 were treated with penicillins for 3 to 5 days. Subsequent GABHS pharyngitis occurred within 30 days in 28 (3.0%) of the 948 siblings in the prophylaxis group and in 26 (5.3%) of the 492 siblings in the control group. Among siblings in the prophylaxis group, subsequent GABHS pharyngitis occurred in 9 (1.8%) of the 507 siblings in the cephalosporin prophylaxis group and in 19 (4.3%) of the 441 siblings in the penicillin prophylaxis group. When these data were each compared with that in the control group (5.3%), a significant statistical difference was seen in the cephalosporin prophylaxis group (P = 0.003) but not in the penicillin prophylaxis group (P = 0.542). Only 5-day cephalosporin prophylaxis showed significant reduction in the rate of subsequent GABHS pharyngitis compared with that in the control group (P = 0.002). Conclusions: In view of the low incidence of subsequent GABHS pharyngitis in the nonprophylaxis group, the usual self-limited nature of GABHS pharyngitis, the cost of prophylaxis and the risk for selecting resistant flora, routine chemoprophylaxis against GABHS pharyngitis for sibling contacts is not recommended.

Comparative study of 5-day and 10-day cefditoren pivoxil treatments for recurrent group A β-hemolytic Streptococcus pharyngitis in children.

Efficacy of short-course therapy with cephalosporins for treatment of group A β-hemolytic streptococcus (GABHS) pharyngitis is still controversial. Subjects were 226 children with a history of at least one episode of GABHS pharyngitis. Recurrence within the follow-up period (3 weeks after initiation of therapy) occurred in 7 of the 77 children in the 5-day treatment group and in 1 of the 149 children in the 10-day treatment group; the incidence of recurrence being significantly higher in the 5-day treatment group. Bacteriologic treatment failure (GABHS isolation without overt pharyngitis) at follow-up culture was observed in 7 of the 77 children in the 5-day treatment group and 17 of the 149 children in the 10-day treatment group. There was no statistical difference between the two groups. A 5-day course of oral cephalosporins is not always recommended for treatment of GABHS pharyngitis in children who have repeated episodes of pharyngitis.