Clinical and immunologic responses to Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in infants injected at 3, 5, 7, and 18 months of age

The safety and immunogenicity of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine (Hib-TT) were evaluated in 77 healthy infants receiving injections at 3, 5, 7, and 18 months of age. No serious local or systemic reactions were noted. After the first injection the geometric mean Hib antibody level rose to 0.55 micrograms/ml, and each subsequent injection elicited a statistically significant rise in the geometric mean. The percentage of vaccinees with Hib antibody levels greater than 0.15 micrograms/ml serum was 75.5% after the first, 97.4% after the second, and 100% after the third Hib-TT injection. This percentage fell to 90.9% at 18 months of age but rose again to 100% after the fourth injection. Control infants (n = 10) injected with diphtheria-tetanus toxoid-pertussis vaccine only had nondetectable levels after the second injection. Hib-TT elicited increases of Hib antibody in all isotypes: IgG greater than IgM greater than IgA. Among IgG subclasses the highest increases were of IgG1. All vaccinated subjects had greater than 0.01 U/ml of TT antibody (estimated protective level) throughout the study. We conclude that Hib-TT, injected at 3, 5, 7, and 18 months, is safe and induces protective levels of antibodies during the age of highest incidence of meningitis caused by Hib.     

Subnormal serum concentrations of IgG2 in children with frequent infections associated with varied patterns of immunologic dysfunction

To characterize more fully the immunologic basis for increased susceptibility to infection in patients with low serum concentrations of IgG2, we identified eight infection-prone children, 1 to 2 years of age, with serum IgG2 concentrations greater than 2 SD below the mean for age and followed their serologic and clinical courses for 1 to 3 years. Two of the eight children became clinically and immunologically normal and may have had transient IgG2 deficiency with an exaggerated developmental delay of this late-maturing subclass. The remaining six subjects had persistently subnormal or low-normal serum IgG2 levels and continued to experience frequent infections. All six of these children responded poorly to Haemophilus influenzae type b (Hib) polysaccharide, and four of six responded poorly to Streptococcus pneumoniae type 3 polysaccharide. Both IgG1 and IgG2-specific antibody responses to these vaccines were abnormal. Three of these six children also responded poorly to tetanus toxoid, an antigen that normally induces a predominant IgG1 response. Although five of these six children produced antibodies in response to Hib polysaccharide protein conjugate vaccine, three of four given Hib oligosaccharide CRM conjugate vaccine required booster doses to respond, a pattern of response characteristic of infants less than 6 months of age. Further, although serum concentrations of IgG1 were normal, peripheral blood mononuclear cells from four of six children tested produced extremely small amounts of IgG1 and IgG3 as well as IgG2. Finally, varied patterns of abnormalities of IgG, IgA, IgM, and IgG4 became apparent in five of the six children with persistently low serum IgG2 values. This study demonstrates that subnormal serum concentrations of IgG2 may be associated with varied patterns of immunologic dysfunction, some of which are evolving and may be responsible for increased susceptibility of these children to infection.     

小儿包虫病免疫球蛋白及IgG亚类抗体检测的诊断价值探讨

目的　研究小儿包虫病的免疫诊断方法 ,探索其抗体应答阴性反应原因。方法　采用间接ELISA和单克隆双抗体夹心ELISA方法 ,对 1998年 5月至 2 0 0 2年 5月新疆自治区人民医院普外科 5 5例小儿包虫病患儿血清的IgG及亚类IgG1、IgG2 、IgG3 、IgG4和IgA、IgM、IgE类抗体及抗原和循环免疫复合物 (CIC)进行检测。 结果　 8种抗体检查方法中IgG1亚型抗体检测的敏感性和特异性最好 ;15例IgG抗体阴性患儿中 ,有 12例分别检测出IgG亚类和 (或 )IgM、IgA、IgE ,有 3例患儿血清各种抗体均呈阴性反应 ;患儿IgM抗体阳性率高于成人 ;IgG1分别与其它种抗体联合检测 ,以IgG1 IgA IgM检出率最高 ;IgG阴性小儿患者血清的循环抗原和CIC阳性率分别为 4 0 %及 2 6 6 7%。结论　IgG1 IgA IgM抗体联合检测方法可提高小儿包虫病免疫诊断的敏感性。抗包虫总IgG抗体表达水平低下、抗体表达种类不同及CIC的形成 ,是造成包虫病患儿IgG抗体反应阴性的主要原因     

AUTOANTIBODIES TO TAMM-HORSFALL GLYCOPROTEIN IN CHILDREN WITH RENAL DAMAGE ASSOCIATED WITH URINARY TRACT INFECTIONS

Abstract. Fasth, A., Bjure, J., Hellström, M., Jacobsson, B. and Jodal, U. (Departments of Pediatrics, Clinical Immunology, Pediatric Clinical Physiology and Pediatric Radiology). Autoantibodies to Tamm-Horsfall glycoprotein in children with renal damage associated with urinary tract infections. Acta Paediatr Scand, 69: 709, 1980.—Autoantibodies to the Tamm-Horsfall (TH) protein were analyzed in sera from 116 patients with pyelonephritis. The increases in antibody levels were limited in 23 patients with radiological detected renal damage during 31 attacks of acute pyelonephritis. 8 children with abnormally low total and/or unilateral ⁵¹Cr EDTA clearance had significantly lower IgG antibody levels to TH protein, than 14 children with normal clearance rate. All 61 children with renal damage had significantly low IgG, IgA and IgM antibody levels to TH protein 6 months after last infection as compared to the reference group. For IgG antibodies, the mean was well below –2 S.D. 12 children with increased serum creatinine had significantly lower IgG antibody levels than those with normal creatinine. No correlation was found between antibody levels and vesico-ureteric reflux. In contrast, 55 children with no renal damage still had significantly increased IgG and IgA antibody levels to TH protein 6 months after the infection. The mechanism for the low antibody levels was discussed and it was concluded that patients with urinary tract infection and low IgG antibody levels to TH protein were at risk for renal damage and should be radiologically examined.     

Serum and salivary antibody responses to non-capsular Haemophilus influenzae antigens in children with meningitis and epiglottitis

Serum IgG, IgA and IgM antibody and salivary IgA antibody concentrations to non-capsular Haemophilus influenzae antigens were measured in 13 children with H. influenzae type b meningitis and in 15 children with epiglottitis. Most had detectable serum IgG and IgM antibody at presentation but significantly fewer patients with meningitis had serum IgA antibody at presentation ( P <0.05). Serum antibody concentrations had risen significantly by 3 weeks after presentation in patients with epiglottitis only. Convalescent serum IgG antibody concentrations against these antigens were higher in younger children with epiglottitis.
Salivary IgA antibody to H. influenzae was detectable at presentation in all children with epiglottitis and in 12 of 13 with meningitis. Salivary antibody concentrations did not differ significantly between the two patient groups at presentation, although patients with meningitis had higher salivary IgA antibody concentrations than 10 children of similar age with bronchiolitis ( P <0.02). There was no association between the presence of salivary antibody and low concentrations of convalescent serum antibody.
The rise in convalescent serum antibody concentrations to non-capsular H. influenzae antigens only in children with epiglottitis is similar to findings for antibody to capsular polysaccharide. However, this rise was greater for IgG in younger patients, and the low titre of convalescent serum antibody in patients with meningitis was not associated with higher titres of IgA antibody in secretions as described by others for polysaccharide antibody. These findings suggest that the poor serum antibody response to these antigens in patients with meningitis is independent of age and is not due to mucosal induction of systemic tolerance.     

Serum immunoglobulins in children perinatally exposed to human immunodeficiency virus

OBJECTIVE: Hypergammaglobulinemia is an early manifestation of perinatal HIV infection. Our objective was to analyze the differences in serum immunoglobulin levels between infected and seroreverter children and their association with clinical outcome. METHODS: We carried out a historical prospective study with 107 infected and 90 seroreverter children. We compared the IgA, IgG, and IgM levels between infected and seroreverters in the first 18 months of life; IgA, IgG, and IgM as surrogate markers of infection; and IgA, IgG, and IgM levels in the first 5 years in infected children, according to clinical outcome. The Mann-Whitney test was used for comparison between groups. Surrogate markers were assessed according to sensitivity, specificity, positive and negative predictive values, and J index. RESULTS: Infected children, when compared to seroreverters, showed significantly higher levels of: IgM from the 1st to the 5th trimester; IgA and IgG from the 2nd to the 6th trimester (P /= 90 mg/dl in the 2nd trimester and IgG >/= 1,700 mg/ dl or 1,200 mg/dl in the 2nd and 3rd trimesters were associated with HIV infection with J indexes of 0.97, 0.92, and 0.93, respectively. Infected children in the B and C categories, compared to those in the N and A, showed higher levels of IgM from the 2nd to the 4th year, and IgA from the 3rd to the 5th year (P 相似文献   

Serum and salivary antibody responses to non-capsular Haemophilus influenzae antigens in children with meningitis and epiglottitis

Serum IgG, IgA and IgM antibody and salivary IgA antibody concentrations to non-capsular Haemophilus influenzae antigens were measured in 13 children with H. influenzae type b meningitis and in 15 children with epiglottitis. Most had detectable serum IgG and IgM antibody at presentation but significantly fewer patients with meningitis had serum IgA antibody at presentation (P less than 0.05). Serum antibody concentrations had risen significantly by 3 weeks after presentation in patients with epiglottitis only. Convalescent serum IgG antibody concentrations against these antigens were higher in younger children with epiglottitis. Salivary IgA antibody to H. influenzae was detectable at presentation in all children with epiglottitis and in 12 of 13 with meningitis. Salivary antibody concentrations did not differ significantly between the two patient groups at presentation, although patients with meningitis had higher salivary IgA antibody concentrations than 10 children of similar age with bronchiolitis (P less than 0.02). There was no association between the presence of salivary antibody and low concentrations of convalescent serum antibody. The rise in convalescent serum antibody concentrations to non-capsular H. influenzae antigens only in children with epiglottitis is similar to findings for antibody to capsular polysaccharide. However, this rise was greater for IgG in younger patients, and the low titre of convalescent serum antibody in patients with meningitis was not associated with higher titres of IgA antibody in secretions as described by others for polysaccharide antibody. These findings suggest that the poor serum antibody response to these antigens in patients with meningitis is independent of age and is not due to mucosal induction of systemic tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical and immunologic responses to the capsular polysaccharide of Haemophilus influenzae type b alone or conjugated to tetanus toxoid in 18- to 23-month-old children

The safety and immunogenicity of Haemophilus influenzae type b (Hib) capsular polysaccharide (CPS) alone, or covalently bound to tetanus toxoid in saline solution (Hib-TT) or adsorbed onto AI(OH)3 (Hib-TT ads), were evaluated after one injection into 18- to 23-month-old healthy children in Sweden. No side reactions were elicited by Hib CPS; side reactions elicited by the two conjugates were similar and comparable to those reported for diphtheria and tetanus toxoids adsorbed. Hib-TT was the most immunogenic of the three vaccines, eliciting about 10-fold higher antibody levels than Hib CPS; of 28 vaccinees, all had greater than 1.0 microgram Ab/mL serum after immunization with Hib-TT. Increases of Hib CPS antibodies within immunoglobulin classes induced by the three vaccines were, in decreasing order, IgG greater than IgM greater than IgA. Within IgG subclasses, rises in IgG1 Hib CPS antibodies were the most frequent, followed by IgG2; some vaccinees with high postimmunization levels also had rises in IgG3 and one in IgG4. Immunization-induced Hib CPS antibodies were bactericidal. Hib-TT also elicited higher levels of tetanus toxoid antibodies than Hib-TT ads; these tetanus toxoid antibodies neutralized tetanus toxin in vivo.     

Intensive treatment for childhood acute lymphoblastic leukemia reduces immune responses to diphtheria, tetanus, and Haemophilus influenzae type b

OBJECTIVES: Immunity to diphtheria toxoid (D), tetanus toxoid (T), and Haemophilus influenzae type b (Hib) is affected in children with acute lymphoblastic leukemia (ALL). The aims were to examine immunity and to compare the response to immunization at 1 or 6 months after treatment. METHODS: Thirty-one patients were immunized with DT and conjugated Hib vaccine (ActHib) at 1 month or 6 months after treatment of ALL with the NOPHO 92 protocol. Antibody levels were determined before and 3 weeks after vaccination. Specific T and Hib antibody-secreting cells of IgG/IgA/IgM isotypes were analyzed in peripheral blood using an ELISPOT technique. RESULTS: All specific antibody levels decreased during ALL treatment, and protective levels after treatment were noted for 17% against D, 33% against T, and 100% against Hib. No high-risk patient had full D or T protection after treatment. After vaccination all the standard- and intermediate-risk patients achieved full protection against D, T, and Hib. The high-risk group showed insufficient immune response (full protection after vaccination: D 56%, T 22%, Hib 78%). No difference was found between vaccination at 1 month or 6 months after treatment. The poor antibody production in the high-risk group correlated to low numbers of antibody-secreting cells. CONCLUSIONS: Nonprotective antibody levels against D, T, and Hib after childhood ALL are more common than previously thought. Insufficient immune response was restricted to the high-risk group and was related to a low number of memory B cells in this study. Immunizations should be included in follow-up after childhood ALL, and the policy should be adapted to treatment intensity.     

Protective immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in children who failed to respond to prior invasive H. influenzae type b disease

A polyribosylribitol phosphate (po1ysaccharide)-tetanus protein conjugate vaccine (PRP-T) against Haemophilus influenzae type b (Hib) was evaluated for protective immunogenicity in 25 previously PRP-unim-munized children who had failed to develop protective PRP antibody levels (< 1 μg/ml) after prior invasive Hib disease at median age 10 months. Children under 21 months of age at time of PRP-T immunization received one, two or three doses. Serum was obtained for total PRP antibody, complement mediated bactericidal activity and specific IgG₁ and IgG₂ PRP antibodies before (n = 25), 1 to 2 months (n = 24) and > 5 months (n = 13) after completed vaccination. One to 2 months after immunization, all but one patient developed > 1 μg/ml of antibody (geometric mean level 50.7 μg/ ml). The non-responder developed protective antibody levels when tested at 6 months after vaccination. Twenty out of 22 sera had detectable complement mediated bactericidal activity (median dilution titer 1:24), 1-2 months after vaccination. Three patients failed to demonstrate PRP antibodies in the IgG₁ or IgG₂ subclasses, although two of them had protective (> lμg/ml) total antibody levels. The second post immunization sera showed persistence of the total PRP antibody levels (geometric mean level 38.2 μg/ml) as well as of the bactericidal activity (median dilution titer 1:32). Conclusion: PRP-T conjugate vaccine is able to elicit a protective immune response in children who have low or unmeasurable PRP antibody levels after a systemic Hib infection.     

Plasma Antibodies to Cow's Milk Are Increased by Early Weaning and Consumption of Unmodified Milk, but Production of Plasma IgA and IgM Cow's Milk Antibodies Is Stimulated Even during Exclusive Breast-Feeding

ABSTRACT. We measured levels of cow's milk-specific (CM) antibodies of immunoglobulin classes G, A and M by enzyme-linked immunosorbent assay in plasma of 198 healthy infants; a variable number of samples taken at birth and at ages of 2, 4, 6, 9, 12 and 28 months were available (altogether 765 samples). The rise in the level of IgG CM antibodies was highest and most rapid in infants exposed to CM formula before the age of 1 month. The level fell by 9 months, but rose again by 12 months. This second rise was attributed to the introduction of dairy milk. Partially breast-fed and fully weaned infants had similar levels of IgG CM antibodies. The levels of IgG CM antibodies were unaffected by the infants' own atopy, their heredity for atopy, and the umbilical serum level of IgG CM antibodies. IgA and IgM CM antibodies were absent at birth. Their levels increased similarly in exclusively breast-fed infants and infants fed CM formula. We conclude that plasma IgG antibodies to cow's milk are increased by early weaning and by consumption of unmodified cow's milk. Production of plasma IgA and IgM antibodies to cow's milk is stimulated even during exclusive breast-feeding.     

Natural immunity to Haemophilus influenzae type B in children of Ankara, Turkey

BACKGROUND: Haemophilus influenzae type b (Hib) infection has a high morbidity and mortality rate especially in children under 5 years of age. The incidence of Hib disease in Turkey is not known, and Hib vaccine is not included in the National Immunization Program. The aim of this study was to determine the natural immunity to Hib of children 6-60 months of age living in the Park Health Center region of Ankara, Turkey. METHODS: A total of 270 children were selected by layered random sampling method, and 242 of them (89.6%) participated in the study. A questionnaire was given to the parents of the children who were included in the study and blood samples were taken from those children. Anti-Hib IgG antibody (anti-PRP) level was determined in the serum by using anti-Haemophilus influenzae IgG EIA kit and anti-PRP antibody levels of 0.15 microg/mL and over were accepted as the natural immunity. RESULTS: Natural immunity was determined in 65.3% of the children. A relationship was determined statistically between the history of disease with possible Hib agent and with natural immunity. CONCLUSIONS: The exposure rate of children with Hib was higher than expected, even in children who were just a few months old. Our data revealed that multicentric, national studies should be done to define the burden of Hib disease before making a decision for Hib vaccine to be included in the National Immunization Program.     

Age-specific sero-prevalence of amoebiasis and giardiasis in southern Indian infants and children.

The age-specific sero-prevalence of amoebiasis and giardiasis was estimated in 91 pediatric diarrhoea and in 70 non-diarrhoeal cases from Southern India. Anti-amoeba/giardia IgG assays on 20 children with inflammatory bowel disease from the UK yielded base-line levels in a non-endemic symptomatic population. IgG, IgM, and IgA levels were estimated to E. histolytica and G. lamblia using an ELISA. Concomittant faecal examinations were done for the Indian children. There was a significant correlation between acquisition of sero-positivity and age. A rise in the IgG response to both organisms was evident between 38 and 47 and 13-24 months, respectively, in diarrhoeal and non-diarrhoeal cases. An appreciable IgM response occurred predominantly in diarrhoea cases and at a younger age (less than 24 months). IgA responses were low. Anti-protozoal IgG levels in the UK children were negligible. There was no relationship between faecal excretion and sero-positivity. The study shows an age-related antibody response to E. histolytica and G. lamblia.     

IgG2 deficiency in children with human immunodeficiency virus infection

Infection with the human immunodeficiency virus (HIV) induces a polyclonal B-cell activation. Despite elevated serum immunoglobulin levels, a significant deterioration of the antigen specific humoral immune response exists in most cases. We studied the influence of HIV infection on the serum levels of IgG subclasses in children. We investigated 76 children (aged 15 months to 18 years) with HIV-1-infection. Most children (88%) showed elevated serum immunoglobulin levels. IgA (87%) and IgM (74%) were more often above normal levels for age than IgG (60%). IgG subclass serum levels were significantly altered. The increase in total IgG was mainly due to a marked augmentation of the IgG1 fraction. In most cases IgG3 was simultaneously elevated. Ten children (13%) had very low IgG4 levels (<0.03 g/l). Out of 61 patients older than 2 years 8 (13%) had a profound IgG2 deficiency with normal or elevated total IgG. Four of them also had low IgG4 levels (<0.03 g/l). A correlation between IgG2 deficiency and HIV infection according to the Centres for Disease Control classification for acquired immunodeficiency syndrome could not be demonstrated (three patients with symptomatic and five with asymptomatic infection).     

Antibodies to group B streptococci in neonates and infants

Invasive group B streptococcal (GBS) infections are common in neonates but are rare after the 1st month of life. It is not known why GBS infections have this age distribution which differs from that of invasive infections caused by other encapsulated bacteria. The aim of this study was to test the possibility that serum antibodies against the GBS capsular polysaccharides (CPS) are acquired during the first months of life thereby preventing infections after the neonatal period. Cord sera were collected from 321 healthy term newborns. A second blood sample was collected at 2, 4, 8, 13 or 26 weeks of age. IgG CPS antibodies (measured by ELISA) against serotypes Ia, II and III were present in 98%–100% of all cord sera and decreased continuously during the first 6 months of life. No IgM antibodies against serotype III CPS were present in cord sera. Only 16%–17% of the children acquired IgM antibodies against serotype III CPS at 3 and 6 months of age. Conclusion Early acquisition of IgG or IgM antibodies against CPS of the most common GBS serotypes was not demonstrated and cannot explain the rare occurrence of invasive GBS infections in children after the 1st month of life. Received: 8 April 1997 and in revised form: 16 September 1997 / Accepted 16 September 1997     

Persistence of serum antibodies elicited by Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in infants vaccinated at 3, 5 and 12 months of age

Eighty-five children received three injections of a vaccine consisting of Haemophilus influenzae type b (Hib) capsular polysaccharide (CPS) conjugated to tetanus toxoid (TT) (Hib-TT) at 3, 5 and 12 months of age according to the vaccination schedule for Swedish children. Diphtheria-tetanus toxoid vaccine was concurrently injected at another site. Two dosages, 7.5 and 15 micrograms, of Hib CPS were studied. No serious reactions occurred. Hib-TT elicited fewer local reactions than diphtheria-tetanus toxoid vaccine. Significant increases in Hib CPS serum antibodies occurred after all injections in both dosage groups with virtually no differences between the two groups. After the first and second injections geometric mean serum antibody concentrations of both dosage groups combined increased to 0.49 and 3.71 micrograms/ml and 81 and 99% of the vaccinees, respectively, had concentrations greater than 0.15 micrograms/ml. After the third dose geometric mean concentrations increased to 13.7 micrograms/ml and all had concentrations greater than 0.15 micrograms/ml. The geometric mean Hib CPS antibody concentrations decreased to 1.24 micrograms/ml 18 months after the third injection, but 97% still had concentrations greater than 0.15 micrograms/ml. The rise of Hib CPS antibodies was mostly in the IgG class. The most pronounced increase was seen in the IgG1 subclass but there were also increase in IgG2 and IgG3. Protective concentrations of TT antibodies were found in all postimmunization sera. In conclusion Hib-TT is safe and immunogenic in infants and should be protective from 6 to 30 months and probably longer thereafter.     

Helicobacter pylori colonization in early life

Helicobacter pylori infection is a major cause of upper gastrointestinal disease throughout the world. Colonization begins in childhood, although little is known about its age of onset, rate, or mode of colonization. Our aim was to identify the age of acquisition of H. pylori colonization in Gambian children. A cohort of 248 Gambian children aged 3 to 45 months was studied at intervals of 3 months for 2 years, using the 13C-urea breath test, specific IgM and specific IgG serology. The prevalence of positive breath tests rose from 19% at 3 months of age to 84% by age 30 months. Elevated specific IgG and IgM antibody levels were associated with positive breath tests, although there was discrepancy between breath test results and serology, particularly IgG serology, during the 1st year of life. Neither IgG nor IgM serology could be validated as reliable diagnostic tools for infant H. pylori colonization compared with the 13C-urea breath test. Reversion to negative breath test, in association with declining specific antibody levels, occurred in 48/248 (20%) of children. On the assumption that the 13C-urea breath test is a reliable index of H. pylori colonization, we conclude that the infection is extremely common from an early age in Gambian children. Transient colonization may occur. Previous studies relying on serodiagnosis may have significantly underestimated the true early prevalence of colonization in the developing world, where the target age for intervention studies is probably early infancy.     

Humoral immunity in children with proven bronchiectasis, bronchial deformations and chronic bronchitis

In 70 children with defined chronic chest disease, immunoglobulins, IgG subclass levels and antibody concentrations specific for Haemophilus influenzae b (Hib), and pneumococcal antigen, were related to disease severity. Bronchological examinations revealed 30 children with chronic bronchitis, 21 with bronchial deformations and 19 with bronchiectasis. Of the 70 children 12 (17.1%) showed an underlying immunodeficiency. The commonest finding was an IgG subclass deficiency, 7 were IgG₂ and 1 IgG₃ deficient, followed by IgA deficiency in 3 patients. All patients had normal IgG and IgM levels except one who had immunodeficiency with elevated IgM. Pneumococcal antibody levels were found to increase between patient groups in the order healthy children < chronic bronchitis < bronchiectasis < bronchial deformations (p < 0.01), but this was not the case for Hib antibodies. We found no selective deficiency of pneumococcal and Hib antibodies in our patients. Pathogens were detected in bronchial cultures from 10% of patients with chronic bronchitis, 33% of those with bronchial deformations and in 63% with bronchiectasis. This increase (p < 0.01) reflects a more severe inflammation of the respiratory tract in such patients. However, immunodeficiencies were equally distributed between patient groups. We conclude that only a subgroup of children with chronic chest disease have an underlying immunodefiency, but most patients (83%) do synthesize normal or even high antibodies in the presence of a bacterial load.     

Effectiveness of Haemophilus influenzae B-diphtheria conjugate vaccination in German children]

BACKGROUND: In 1990 the Haemophilus influenzae b-Diphtheria conjugate vaccine (Hib-D) was introduced in Germany. In addition, most children under 18 months of age failed to develop protective levels of Hib antibodies in response to systemic infections. METHODS: To evaluate the protective efficacy of the Hib-D vaccine in Germany a post marketing case-control study was performed during 1.5. 1990-30.4. 1992. Surveillance for invasive Hib-infections was maintained by pediatricians of 8 hospitals in the Rhein-Main area. The antibody responses to Hib were evaluated by ELISA at the onset (days 0-3) and during remission of disease. RESULTS: During the first year of the study 23 cases per 100,000 children of invasive Hib-infections were recorded. Of these children, 15 suffered from meningitis, 6 from epiglottitis and one from cellulitis and pericarditis respectively. None of these patients had been vaccinated except for one, who received two injections of Hib-D. Due to increased acceptance of the Hib-D vaccine we found a significant reduction of invasive Hib-infections (6 cases per 100,000 children) in the second year of the study. Again, of these children only one child was vaccinated. As expected, in all patients investigated the initial Hib antibody level was below 1 microgram/ml. The development of Hib specific immunity to invasive disease was clearly age dependent: 10 of 11 children below 18 months failed to produce any Hib antibodies (> 0.15 microgram/ml) in response to their infection. In contrast 8 of 10 children older than 18 months developed protective antibody levels to Hib. CONCLUSIONS: The incidence of serious Hib-disease has significantly decreased in Germany since the introduction of the Hib-D vaccine. Because no other Hib vaccine was licensed in Germany our data confirm efficacy and safety of Hib-D reported previously. In addition, children, who contracted disease before 18 months of age, remain susceptible to Hib and require active immunization for protection.     

Lack of correlation between infection with reovirus 3 and extrahepatic biliary atresia or neonatal hepatitis

Infection with reovirus 3 (Reo-3) has been suggested as the cause of extrahepatic biliary atresia and idiopathic neonatal hepatitis, but confirmation has been lacking. Therefore we have searched for a specific anti-Reo-3 antibody response in the sera of patients with biliary atresia or neonatal hepatitis and for Reo-3 antigens in their hepatobiliary tissues. Sera from 23 infants with extrahepatic biliary atresia, 12 with neonatal hepatitis, 30 age-matched control patients with other liver diseases, and 55 control patients without liver disease were tested by an enzyme-linked immunosorbent assay for total (IgA, IgG, and IgM) anti-Reo-3 antibodies; sera of infants younger than 6 months of age were tested also for IgM anti-Reo-3 antibodies alone. There was no difference between either total or IgM anti-Reo-3 antibody levels in infants with extrahepatic biliary atresia or neonatal hepatitis and levels in control infants. Reo-3 antigens were not detected in the hepatobiliary tissues of 19 infants (18 with biliary atresia, one with neonatal hepatitis) by an immunoperoxidase method that readily demonstrated Reo-3 in control infected HEp-G2 cells. Our data do not support a relationship between neonatal liver diseases and infection with Reo-3.