Antitoxin Antibody Levels Research Articles

Toxic Shock Syndrome following Septoplasty: Report of 2 Cases and Literature Review

Objectives: Toxic shock syndrome (TSS) is a rare but potentially life-threatening multisystem disease. Reported incidence after nasal surgery is 16.5 per 100,000 operations. We report 2 such cases from Northern Ireland occurred over last 8 years (2006 and 2012). Diagnostic criteria, pathogenesis, and management of TSS are discussed. Methods: Case 1: A 19-year-old man developed sudden severe facial swelling, fever, diffuse erythroderma, tachycardia, and hypotension 16 hours after routine septoplasty and cautery to inferior turbinates. He had sialastic internal nasal splints and calcium alginate packing. Initially anaphylaxis to latex or diclofenac was suspected but disproved by lab investigations. He had surgical tracheotomy to protect airway from progressive facial cellulitis. Nasal swab confirmed grown staphylococcus aureus (TSST-1 producing-strain), and he recovered slowly with antibiotics. Case 2: A 24 year- old man developed a mild form of TSS 36 hours post-surgery after routine septopasty and Merocel packing, with nausea, hypotension, tachycardia, fever, and erythroderma. TSS was promptly suspected. The patient moved to intensive care for supportive care of refractory hypotension, and he made a slow recovery with antibiotics. Nasal swab had grown staphylococcus aureus. (TSST-1 strain). Results: TSS cases following nasal surgery have been associated with nasal packing, mucosal barrier violation, and prior colonization of toxic-shock-syndrome-toxin-1 (TSST-1) strain as well as low antitoxin antibody levels. Hence TSS requires nasal carriage of a toxigenic strain of staphylococcus aureus by a susceptible patient. Topical or systemic antibiotics did not have a demonstrable protective effect. Conclusions: Early recognition and prompt intervention minimize the morbidity and mortality associated with this disease.

Kinetics of Local and Systemic Immune Responses after Vaginal Immunization with Recombinant Cholera Toxin B Subunit in Humans

Vaginal vaccination seems to be the best strategy for inducing specific immunoglobulin A (IgA) and IgG antibody responses in the female genital tract. The relative efficiencies of one, two, and three vaginal doses of recombinant cholera toxin B subunit (CTB) in generating mucosal and systemic immune responses in healthy women were evaluated, and the kinetics of the immune responses were monitored for responding volunteers for up to 12 months after the last vaccination. A single dose of CTB failed to generate CTB-specific IgA antibody responses in cervical secretions. Two vaccinations induced significant increases in IgA antitoxin titers in seven of nine volunteers, and four volunteers also developed IgG antitoxin responses. The magnitudes of the responses were 20-fold for IgA antitoxin and 7.1-fold for IgG antitoxin. A third vaccination did not significantly increase the antitoxin responses, although the frequency of IgG responses was slightly higher than that after the second vaccination. In serum, CTB-specific antibodies were observed already after a single vaccination. However, two vaccinations were required to induce marked IgA as well as IgG antitoxin titer increases in the majority of volunteers. The postvaccination levels of antitoxin antibodies in serum were comparable after two and three vaccinations. At 12 months after vaccination, significantly elevated IgA and IgG antitoxin levels in cervical secretions could still be detected in approximately half of the volunteers who had initially responded to the vaccine. Antitoxin titer increases in serum were found in most of the vaccinees at follow-up.

Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea

Recurrent C difficile -associated diarrhea (CDAD) is associated with a lack of protective immunity to C difficile toxins. A parenteral C difficile vaccine containing toxoid A and toxoid B was reported previously to be safe and immunogenic in healthy volunteers. Our aim was to examine whether the vaccine is also well tolerated and immunogenic in patients with recurrent CDAD. Subjects received 4, 50-microg intramuscular inoculations of the C difficile vaccine over an 8-week period. Serum antitoxin antibodies were measured by ELISA, and toxin neutralizing activity was evaluated using the tissue culture cytotoxin assay. Three patients with multiple episodes of recurrent CDAD were vaccinated. Two of the 3 showed an increase in serum IgG antitoxin A antibodies (3-fold and 4-fold increases, respectively) and in serum IgG antitoxin B antibodies (52-fold and 20-fold, respectively). Both also developed cytotoxin neutralizing activity against toxin A and toxin B. Prior to vaccination, the subjects had required nearly continuous treatment with oral vancomycin for 7, 9, and 22 months, respectively, to treat recurrent episodes of CDAD. After vaccination, all 3 subjects discontinued treatment with oral vancomycin without any further recurrence. A C difficile toxoid vaccine induced immune responses to toxins A and B in patients with CDAD and was associated with resolution of recurrent diarrhea. The results of this study support the feasibility of active vaccination against C difficile and its toxins in high-risk individuals but must be validated in larger, randomized, controlled trials.

Antibodies to highly conserved peptide sequence of staphylococcal and streptococcal superantigens in Kawasaki disease

Superantigen-mediated disease such as toxic shock syndrome is seen in patients who have a weak antibody response to the antigen toxic shock syndrome toxin 1 (TSST-1). We hypothesized that there may be deficiency in antibody production to staphylococcal and streptococcal toxins in Kawasaki disease (KD) children. A peptide was constructed from the homologous portion of the staphylococcal enterotoxins (SE) and streptococcal pyrogenic enterotoxins (SPE), and antibodies to the peptide were made. The anti-peptide antibody immunoblotted several of the SE toxins and SPE toxins. Presence of the peptide antibodies was investigated via ELISA in the sera of acute KD ( n = 30), convalescent KD ( n = 12), control adults ( n = 10), and children ( n = 19). The mean anti-peptide antibodies were indistinguishable between control children and KD before treatment with immunoglobulin ( P = 0.7) but rose significantly after therapy ( P < 0.01). The adults had significantly higher antibodies than the KD, both acute and late ( P < 0.0001) and the control children ( P < 0.0001). Thus, KD patients do not have a defective serological response against toxins such as SPE/SE/TSST-1. Normal children have significantly lower antitoxin antibody levels to the toxins compared to the adults.

Evidence of increased carriage of Corynebacterium spp. in healthy individuals with low antibody titres against diphtheria toxoid.

This study evaluated whether a correlation exists between carriage of corynebacteria and the lack of immunity to diphtheria toxoid. Samples of both nasal and pharyngeal secretions were taken from 500 apparently healthy subjects of both sexes and of all ages and inoculated onto Tinsdale's medium. A serum sample was also taken for ELISA test to determine the titre of diphtheria toxin antibodies. None of the subjects carried Corynebacterium diphtheriae. Ninety-three strains of Corynebacterium spp. were isolated from 93 subjects and 86 of these were classified to species or group level by biochemical tests. C. xerosis was the most common (25.8%) followed by C. pseudodiphthericum (16.1%), C. jeikeium and C. striatum (both 10.8%), and C. urealyticum (9.7%). Three other species accounted for approximately 20% of strains and seven were unclassified as biochemically atypical corynebacteria. Non-protective antibodies to diphtheria toxin were found in 80 of the 93 subjects and a strong statistical association was demonstrated between carriage of corynebacteria and non-protective levels of anti-toxin antibodies. The remaining 13 subjects had protective levels of antitoxin antibodies. In contrast, only 45 of the 407 non-colonized subjects had non-protective antitoxin titres. The prevalence of carriage increased with age among males as did the percentage of non-protected subjects. The prevalence of female carriers of corynebacteria was significantly lower. Serum samples from 12 subjects with different antibody titres to diphtheria toxoid reacted to varying degrees with whole-cell lysates of a number of species of corynebacteria. The results suggest that a causal relationship may exist between nasopharyngeal carriage of corynebacteria and a low anti-diphtheria toxin immune response.

Immune status against diphtheria among immigrants from the former USSR who arrived in Israel during 1990-1991.

Large outbreaks of diphtheria occurred recently in the former USSR. Between 1989 and 1994, a total of about 600,000 Soviet immigrants arrived in Israel. The immune status against diphtheria in a sample of 992 men aged 17-49 and 195 women aged 17-19, who arrived in Israel during 1990-91, was studied in order to evaluate the need for vaccination. Participants completed a self-administered questionnaire and diphtheria antitoxin antibody levels were measured by means of ELISA. At age 17-19, the prevalence of antitoxin antibody levels below the protective level of 0.01 IU/ml was 4.8% in the men and 2.1% in the women. Among the men, the percentage lacking protection declined from 4.8% at age 17-19 years to 1.6% at age 20-24, and increased to 18.2% at age 35-49. In the oldest group, the prevalence of those lacking protection was considerably higher than for the general Israeli population. In the multivariate analysis, age, mother's education and republic of origin were significantly associated with the absence of protection. Immigrants from the former USSR appear to be more susceptible to diphtheria, thus increasing the possibility of clinical disease, and it is recommended that they receive booster doses of diphtheria toxoid.

Mucosal and systemic immunogenicity of a recombinant, non-ADP-ribosylating pertussis toxin: effects of formaldehyde treatment

The effect of formaldehyde treatment on the mucosal and systemic immunogenicity of the geneticallydetoxified pertussis toxin ( PT-9K 129G ) was investigated. Groups of BALB c were immunized intranasally (i.n.) or subcutaneously (s.c.) with untreated, lightly formaldehyde treated (LFT) or heavily formaldehyde treated (HFT) recombinant pertussis toxin (PT) mutant, PT-9K 129G . Intranasal immunization with native PT-9K 129G induced significant levels of anti-toxin antibodies in serum and IgA anti-toxin responses in nasal and lung lavages of these mice. Similar local and systemic responses were observed following intransal immunization with LFT toxin. However, i.n. immunization with HFT toxin failed to induce a local IgA response and elicited a much diminished anti-toxin response in the serum. In contrast, the total antibody response following s.c. immunization was not significantly affected. In addition, i.n. immunization with native PT-9K 129G induced low but detectable levels of toxin neutralizing antibodies in the serum. These results show that native PT-9K 129G protein acts as a mucosal immunogen in mice and that this activity is greatly diminished by HFT of the protein.

Toxic shock syndrome after functional endonasal sinus surgery: An all or none phenomenon?

Reported cases of toxic shock syndrome (TSS) following nasal surgery or functional endonasal sinus surgery (FESS) are uncommon. Classic TSS is a serious multisystem disorder resulting from Staphylococcus aureus phage I toxic shock syndrome toxin 1 (TSST-1), and it is characterized by fever, rash, hypotension, mucosal hyperemia, vomiting, diarrhea, and laboratory evidence of multisystem organ dysfunction. TSS cases following nasal surgery have been associated with nasal packing, mucosal barrier violation, prior S aureus phage I colonization, as well as low antitoxin antibody levels. Of the 1700 FESS procedures performed at our institution, 3 cases were complicated by classic TSS, with 2 additional patients having a postsurgical course compromised by a milder degree of TSS. Diagnostic criteria, clinical presentation, management, and etiology are discussed, and the possibility of a continuum from mild-to-classic TSS is addressed.

Prevalence and correlates of diphtheria toxin antibodies among young adults in Israel

The paucity of information about immunity against diphtheria of young adults in Israel prompted us to analyse sera from a random sample of 480 recruits (263 males and 217 females) aged 18-19 years. Antitoxin antibody levels were determined by means of ELISA. Of the recruits 58.1% had antibody values greater than 0.1 IU/ml; 38.5% had amounts between 0.01 and 0.1 IU/ml, which is considered low when using the ELISA method, and 3.3% had less than 0.01 IU/ml. The results of this study suggest that a booster dose of antidiphtheria vaccine should be given to adults in Israel in order to ensure adequate antibody levels.

Randomized double-blind placebo controlled trial to evaluate the safety and immunogenicity of the live oral cholera vaccine strain CVD 103-HgR in Swiss adults

A randomized, double-blind, placebo controlled trial was conducted in 50 healthy Swiss adults to assess the safety and immunogenicity of the live oral attenuated cholera vaccine candidate strain Vibrio cholerae CVD 103-HgR (classical, Inaba). A single dose of 5 x 10(8) viable CVD 103-HgR organisms, administered in a buffered liquid formulation, was well tolerated as compared with individuals who received an equivalent amount of heat-killed Escherichia coli K-12 placebo. Eighty-eight percent of subjects receiving CVD 103-HgR mounted a significant (greater than fourfold) rise in Inaba vibriocidal titre while 68% did so for the heterologous Ogawa serotype. The magnitude of the vibriocidal antibody response (as measured by peak geometric mean titre and by fold-rise in titre over baseline) was greater for the homologous Inaba serotype. Nineteen out of 25 volunteers (76%) responded with a significant (p less than 0.05) rise in serum antitoxin levels. No vaccinee who received the E. coli K-12 placebo mounted a significant rise in either vibriocidal or antitoxin antibody levels. These results corrobrate the safety and immunogenicity of CVD 103-HgR in healthy adult volunteers.

Immunotherapy in patients with diphtheria

Patients with suspected diphtheria were treated with 600–18,000 IU human antidiphtheria immunoglobulin in 13 cases and with 80,000 IU equine anti-diphtheria immunoglobulin in one case. There were three fatal cases of diphtheria; two attended hospital too late for an expected effect of therapy (> day 5), while one was treated with 10,000 IU human anti-diphtheria immunoglobulin on the third day of disease. Four patients with diphtheria and later neurological complications were given immunotherapy on days 2–4 after the start of the disease. Antitoxin antibody levels, assessed by microculture neutralization test in Vero cells, following therapy with human immunoglobulin did not reach above 2 IU per ml during the first week of disease. The higher dose of equine immunoglobulin resulted in an antitoxin level of 12·8 IU per ml on the second day after therapy. Equine immunoglobulin with higher antitoxin concentration than human immunoglobulin may be the preferable therapy in severe diphtheria.

Pediatric diphtheria and tetanus toxoids-adsorbed vaccine

Diphtheria and tetanus toxoids (DT) vaccine should be given to children at 2, 4 and 6 months of age when there are contraindications to the administration of pertussis vaccine. We have previously reported that such children develop protective antitoxin antibody levels to diphtheria and tetanus antigens. This follow-up study evaluates the decay in antitoxin antibody levels and the booster response elicited to DT antigen when a fourth dose is given at approximately 18 months of age. Twenty-three children receiving DT vaccine were compared to 38 receiving diphtheria and tetanus toxoids-pertussis (DTP) vaccine. The prebooster antibody titer to diphtheria and tetanus at approximately 18 months of age had declined below the recommended protective level in one child who had received DT vaccine and in three children who had received DTP. Following the 18-month booster dose of DT and DTP vaccine, all of the children had protective titers to diphtheria and tetanus toxin. These results suggest that the adjuvant effects of pertussis vaccine are not required to achieve adequate immunization to diphtheria and tetanus when currently available DT vaccine is used in early childhood.

Antitoxin antibody levels and the outcome of illness during an outbreak of diphtheria among alcoholics.

During an outbreak of diphtheria among alcoholics in Göteborg, Sweden, a study was made of the diphtheria-antitoxin antibodies in serum samples from 8 clinical cases and 36 carriers of toxin-producing Corynebacterium diphtheriae. 33/36 carriers were antibody-positive and had antitoxin titres greater than 0.01 IU/ml, a level which is regarded as relative protective, while only 1/8 clinical cases had such a titre. This patient presented a mild illness with no complications. The results of the study of this outbreak stress the importance of maintaining adequate antibody levels against diphtheria in highly developed societies.

The immunology of tetanus.

The results of measurements made in two cases of tetanus suggest that the level of tetanus antibody in the blood cannot be used as a diagnostic test for the disease. The investigation also indicated that an attack of tetanus does not result in a rise in tetanus antitoxin antibody levels. This confirms the opinion that tetanus is not an immunising disease. In the cases described, the pseudocholinesterase level was not of diagnostic value.