Detection of Haemophilus Influenzae Type B Antigen in Cerebrospinal Fluid After Immunization

Darville, Toni; Rf, Jacobs; Ra, Lucas; Caldwell, Burton V.

doi:10.1097/00006454-199203000-00017

Cited by 13 publications

(5 citation statements)

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“…The induction and effector sites of these mucosal immune responses are unclear. It is possible that the PS antigen is absorbed into the body and transported to lymphoid tissue local to the upper respiratory tract, as injected Hib PS antigen has been shown to be dispersed in the body (8,31). Another possibility is that B cells are stimulated in the lymphoid tissues near the antigen injection site and then migrate to the upper respiratory mucosa and produce IgA antibodies there (5,7,26).…”

Section: Discussionmentioning

confidence: 99%

Mucosal Immune Responses to Meningococcal Group C Conjugate and Group A and C Polysaccharide Vaccines in Adolescents

et al. 2000

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Previous studies in children have shown that Haemophilus influenzae type b (Hib) polysaccharide conjugate vaccines can reduce nasopharyngeal carriage of H. influenzae and provide herd immunity and suggest that this effect is mediated through mucosal antibodies. As this phenomenon may operate in other invasive bacterial infections which are propagated by nasopharyngeal carriage, mucosal antibody responses to meningococcal C conjugate and A/C polysaccharide vaccines were investigated. A total of 106 school children aged 11 to 17 years were randomized to receive a single dose of either conjugate or polysaccharide vaccine in an observer-blind study. Before and at 1, 6, and 12 months after immunization, samples of unstimulated saliva were collected and assayed by enzyme-linked immunosorbent assay for group C polysaccharide-specific immunoglobulin A (IgA), IgA1, IgA2 and secretory component, IgG antibodies, and total IgG and IgA. A subset of serum samples were also assayed for specific IgA and IgG antibodies. The concentrations of specific IgA and IgG in saliva were expressed both as nanograms per milliliter and as nanograms per microgram of total IgA or IgG. One month after immunization, significant increases in antibody titers (both IgA and IgG) were observed in saliva in both groups. There were significant subsequent falls in antibody titers by 6 months. Anti-meningococcal C-specific secretory component and IgA antibody titers were closely correlated (r ‫؍‬ 0.85, P < 0.001), but there was no significant correlation between salivary and serum IgA titers, suggesting that IgA antibodies are locally produced. Significant correlation was found between salivary and serum IgG titers (r ‫؍‬ 0.52, P < 0.01), suggesting that salivary IgG may be serum derived. Compared with polysaccharide vaccine, the conjugate vaccine induced significantly higher salivary IgG responses (P < 0.05), although there were no significant differences between salivary IgA responses to the two vaccines. The conjugate vaccine induced greater salivary IgG responses than a polysaccharide vaccine. Both vaccines induced significant salivary IgA antibodies. Further studies are needed to establish the functional significance of these mucosal responses.The increased incidence of septicemia and meningitis due to group C Neisseria meningitidis in recent years in the United Kingdom, particularly among older children and young adults, has created considerable public concern (30). Currently licensed polysaccharide vaccines against group C meningococcal disease do not induce immunological memory and are poorly immunogenic in children under the age of 2 years (4, 13, 21). New conjugate vaccines have been shown to induce greater immunoglobulin G (IgG) and bactericidal antibody responses (S. Choo, Q. Zhang, J. Everard, C. Goilav, E. Hatzmann, J. Zuckermann, and A. Finn, Arch. Dis. Child 80:A71, abstr. G207, 1999), to be immunogenic in infants, and to induce immunological memory (11,(22)(23)(24)34).Haemophilus influenzae type b (Hib) conjugate vaccines have been used ...

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Section: Discussionmentioning

confidence: 99%

Mucosal Immune Responses to Meningococcal Group C Conjugate and Group A and C Polysaccharide Vaccines in Adolescents

et al. 2000

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“…However, this raises the question, where would the antigen presentation take place? Parenterally injected Hib PS is known to be dispersed in the body [34, 35]. It can be speculated that PS antigen leaks, for example, to the tonsils and stimulates local antibody‐secreting cells there.…”

Section: Discussionmentioning

confidence: 99%

Subclass distribution of IgA antibodies in saliva and serum after immunization withHaemophilus influenzaetype b conjugate vaccines

Kauppi-Korkeila

Saarinen

Eskola

et al. 1998

Clinical and Experimental Immunology

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SUMMARYIgA subclass distribution of antibodies against capsular polysaccharide (PS) of Haemophilus influenzae type b (Hib) was studied in saliva and serum samples of children vaccinated with two (n ¼ 58) or three doses (n ¼ 53) of Hib vaccine. One month after the second dose of Hib conjugate vaccine, at 7 months old, 40% of the children had IgA1 and 41% had IgA2 anti-Hib PS antibodies in saliva. One month after the third dose, at 15-25 months old, IgA1 was the predominating subclass; 72% of the children had IgA1, 26% had IgA2 anti-Hib PS in saliva. The mean concentration of IgA1 anti-Hib PS, expressed as optical density (OD) values, was significantly higher after three doses (OD 80·7) than after two doses (OD 18·9). The mean concentration of IgA2 did not change significantly after the third dose (OD 23·8 after two doses, OD 18·1 after three doses). In serum, IgA1 anti-Hib PS predominated both after two (17% had IgA1, none had IgA2) and three doses (72% had IgA1, 4% had IgA2) of Hib vaccine. In conclusion, both IgA1 and IgA2 anti-Hib PS were found in saliva of immunized children after two doses of Hib conjugate vaccine, whereas the third vaccine dose induced a shift towards IgA1 anti-Hib PS dominance in saliva.

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“…Goepp et al found that the majority of infants had a positive LA test 2 weeks following Hib-conjugate vaccination and that 41% were still positive at 30 days (15). Immunization with conjugate vaccine may even result in LA-detectable Hib antigen in the CSF (7,36). The declining incidence of invasive Hib disease and the frequency of detection of vaccine antigen resulted in a 100% incidence of false-positive LA tests for Hib in this study.…”

Section: Discussionmentioning

confidence: 45%

“…Several factors, however, limit the clinical utility of bacterial antigen tests and make their routine use controversial. These factors include a decline in the incidence of Hib invasive disease following the advent of specific vaccination (35), imperfect antigen specificity (4,6,8,11,13,21,23,25,28,30,32), misleading positive results due to detection in urine or CSF of circulating Hib antigen after vaccination (7,15,36,43,44), contamination of urine with skin flora (3,40), and, importantly, the common failure of physicians to respond to rapidly generated diagnostic test results (26). In this review of over 5,000 LA tests, we found no evidence of clinical utility to support their current common use and instead found a high incidence of confounding results.…”

Section: Discussionmentioning

confidence: 99%

“…The advent of routine immunization of infants with Hib conjugate vaccines has led to a dramatic decline in the incidence of invasive Hib disease (35) and has changed the operational characteristics of antigen detection assays (7,15,19,36,43,44). In fact, the epidemiologic situation under which the LA tests were developed no longer exists, and their continued use in the changed population is in part responsible for their poor performance.…”

Section: Discussionmentioning

confidence: 99%

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Rapid bacterial antigen detection is not clinically useful

1995

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Latex agglutination (LA) of capsular polysaccharide bacterial antigen is a frequently performed laboratory procedure, but its use is controversial. To assess the clinical utility of this test, we reviewed all LA tests performed over a 10-month period at two sites, a major university-based referral center and a private specialty pediatric hospital. Samples were assayed either individually or as a panel for the group B streptococcus, Streptococcus pneumoniae, Haemophilus influenzae, and three sets of Neisseria meningitidis serogroups (A and Y, C and W135, and B and Escherichia coli K1). Of 5,169 assays performed on 1,268 clinical samples (786 urine and 478 cerebrospinal fluid, 3 pleural fluid, and 1 synovial fluid sample), 57 (1.1%) were positive, including 1.7% of urine and 0.3% of cerebrospinal fluid samples. All LA true-positive cerebrospinal fluid samples showed the causative microorganisms by Gram stain. Detailed chart review of these 57 positive samples showed that the LA result was false-positive in 31 (54%), true-positive in 22 (38%), and indeterminate in 4 (7%) samples. Therapy was not altered on the basis of any of the true-positive LA results. The 31 false-positive results led to additional cost, prolonged hospitalization, and some clinical complications. Total patient charges were $175,000 ($7,954 per true-positive), with no detectable clinical benefit. Our retrospective study does not support the current use of LA for rapid antigen detection. What, if any, specific indications exist for this test remain to be elucidated.

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Detection of Haemophilus Influenzae Type B Antigen in Cerebrospinal Fluid After Immunization

Cited by 13 publications

References 0 publications

Mucosal Immune Responses to Meningococcal Group C Conjugate and Group A and C Polysaccharide Vaccines in Adolescents

Mucosal Immune Responses to Meningococcal Group C Conjugate and Group A and C Polysaccharide Vaccines in Adolescents

Subclass distribution of IgA antibodies in saliva and serum after immunization withHaemophilus influenzaetype b conjugate vaccines

Rapid bacterial antigen detection is not clinically useful

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