Serum antibody response to filamentous hemagglutinin in patients with clinical pertussis measured by an enzyme-linked immunosorbent assay

Titers of antibodies to filamentous hemagglutinin (FHA) were determined by enzymelinked immunosorbent assay in acute and convalescent phase serum samples from 158 patients with clinical symptoms typical of whooping-cough. In 96 of the patients the diagnosis was verified by culture. Significant changes in serum levels of IgG, IgM and/or IgA antibodies against FHA were demonstrated in 126 patients (80%). Thus, demonstration of significant changes in FHA antibody titers in serum can be used for serological diagnosis of pertussis. The results also show that high levels of IgG, IgM and/or IgA antibodies in a single serum sample suggest current pertussis infection, but if the diagnosis is based on determinations of FHA antibody titers in a single serum sample the sensitivity is low. The levels of antibody to FHA were compared with previously determined levels of antibodies to pertussis toxin. A significant antibody response against both FHA and pertussis toxin was seen in 111 patients (70 %) while 147 patients (93 %) developed a significant increase in antibodies against one or both antigens.     

Comparison between radioimmunoassay and direct and indirect enzyme-linked immunosorbent assays for determination of antibodies against Haemophilus influenzae type b capsular polysaccharide.

Levels of antibodies against Haemophilus influenzae type b capsular polysaccharide were determined in acute-phase and convalescent-phase serum samples obtained from 21 children with invasive H. influenzae type b infections and from 44 children vaccinated with two H. influenzae type b vaccines. Amounts of immunoglobulin G (IgG), IgM, and IgA antibodies were measured by direct and indirect enzyme-linked immunosorbent assay (ELISA), and the total amount of antibodies was measured by radioimmunoassay (RIA). Results obtained by ELISA were calculated by multiple-point parallel-line comparison and by endpoint analysis. A very good correlation was obtained between direct and indirect ELISA values. In the lower range of antibody concentrations, the correlation between ELISA values obtained by endpoint analysis and those obtained by multiple-point parallel-line comparison was poor, since the latter method of calculation yielded values of up to 1 microgram/ml in sera that were negative according to endpoint analysis. These sera with negative endpoint titers also had undetectable or very low antibody concentrations as measured by RIA. Consistent with this finding, in acute-phase and prevaccination sera with undetectable or low antibody concentrations as measured by RIA, ELISA values calculated by multiple-point parallel-line comparison were much higher. In sera with higher antibody concentrations, however, parallel-line comparisons showed good correlation between RIA and ELISA values. Although no reference method for measuring true antibody concentrations is available, ELISA values as calculated by multiple-point parallel-line comparison appear to overestimate antibody concentrations in sera containing low antibody concentrations, whereas ELISA values obtained by endpoint analysis are less well correlated with RIA values at higher concentrations.     

Incidence, serogroups and case-fatality rate of invasive meningococcal infections in a Swedish region 1975-1989.

In a retrospective study of invasive meningococcal infections in Greater Gothenburg, Sweden, 213 cases of culture-verified meningitis or septicaemia were identified during the 15-year period 1975-1989. The annual incidence was 2.0/100,000. Cases were seen in all age-groups with the highest rates in the 0-4 and 15-19 year-old groups, 9.5 and 6.2/100,000 respectively. 20% of the patients were less than 2 years. 91% of the patients had no known risk factors. In only 10 cases (5%) was contact with another case of meningococcal infection known. The main clinical manifestations were meningitis (57%), septicaemia with no sign of focal infection (25%) and septic shock (17%). The case-fatality rate for all the patients was 6.6% and did not change during the 15-year period. One-third of the patients who presented with septic shock died. The serogroup was known for strains from 192 patients. 51% of the strains belonged to serogroup B, 10% to group A and 23% to group C. In conclusion, the incidence of meningococcal infection was low but the relatively high case-fatality rate warrants a search for effective prophylaxis. About 30% of the cases were potentially preventable by the currently available tetravalent (A, C, Y and W135) polysaccharide vaccine, which is immunogenic in children greater than 2 years. Widespread use of antibiotic prophylaxis to close contacts of known cases would not lower the incidence markedly.     

Concentrations of ceftazidime,tobramycin and ampicillin in the cerebrospinal fluid of newborn infants

Thirty-five neonates with suspected septicaemia were randomized to treatment with tobramycin or ceftazidime, both in combination with ampicillin. Concentrations of antibiotics in the CSF were measured 1 h after the third, fourth or fifth injection. In 13 of 17 neonates tobramycin CSF concentrations were below 0.5 mg/l. Ceftazidime CSF concentrations ranged from 2.5 to 17 mg/l, which should be sufficient for treatment of infections with group B streptococci and most aerobic gram-negative bacilli but not all strains of Staphylococcus aureus. Ampicillin CSF concentrations ranged from 1 to 80 mg/l, which should be sufficient for treatment of meningitis caused by enterococci and Listeria monocytogenes, the most important neonatal pathogens not covered by ceftazidime.     

Acute epiglottitis in children and adults in Sweden 1981-3.

In a retrospective study of the incidence of acute epiglottitis in Sweden, 485 children and 356 adults fulfilled the following criteria: (a) red and swollen epiglottis visualised at laryngoscopy; (b) stridor or difficulties in swallowing own saliva or water; and (c) temperature greater than or equal to 38 degrees C. The age specific incidence in children (0-14 years) was 10 and in adults (greater than or equal to 15 years) 1.8/100,000/year. These incidence rates were higher than the incidence of Haemophilus influenzae meningitis in the same population. Blood cultures were obtained from 290 children (60%) and 185 adults (52%). H influenzae was isolated from 267 blood cultures (92%) from children and 98 blood cultures from adults (53%). Other organisms were isolated from six adults (3%). An artificial airway was established in 352 children (73%) and in 68 adults (19%); the remainder were treated conservatively. Six children and two adults died. Sweden has a high incidence of acute epiglottitis in children and the disease also occurs in adults. The importance of H influenzae in the aetiology of epiglottitis in all age groups is confirmed, but in adults many cases occur without septicaemia. The mortality is currently very low.     

Clinical, metabolic, and antibody responses of adult volunteers to an investigational vaccine composed of pertussis toxin inactivated by hydrogen peroxide

A toxoid vaccine, composed of purified pertussis toxin inactivated with H2O2 (NICHD-Ptxd), was developed on the basis of evidence that serum neutralizing antibodies (antitoxin) would confer immunity to pertussis. In vivo and in vitro assays of NICHD-Ptxd showed only trace or nondetectable levels of pyrogenic, adenosine diphosphate-ribosyltransferase, binding and pharmacologic activities. Nevertheless, about 40% of the antigenicity of pertussis toxin was retained. Adult volunteers were injected, two times 6 weeks apart, with either 10 (n = 21), 50 (n = 25), or 75 (n = 30) micrograms/dose of one lot, Ptx-06, adsorbed onto AI(OH)3. Neither fever nor changes in the levels of leukocytes, lymphocytes, fasting blood glucose, or insulin were observed in the volunteers. The optimal immunizing dose, 50 micrograms, induced levels of antitoxin (geometric mean (GM) 302 U) comparable to those found in eight adults convalescent from pertussis (GM 269 U) and greater than those found in 18-month-old children after their fourth dose of diphtheria and tetanus toxoids and pertussis vaccine (GM 20.0 U, p less than 0.001). These data indicate that NICHD-Ptxd is safe and immunogenic in adults, and they justify its evaluation in infants and children.     

Clinical course of whooping cough in children younger than six months.

The patient records of 59 children aged 2--26 weeks with culture-verified pertussis were analysed. Twenty-four of them were hospitalized, in most cases for social reasons. Only one child with hypothyroidism and a complicating pneumonia was critically ill. Seventeen of the 35 non-hospitalized patients had a mild disease without developing typical whooping attacks. Thirteen children were treated with erythromycin in the catarrhal stage. There was a tendency towards milder disease in this group but the differences compared to untreated children were not statistically significant.     

Nineteen cases of persistent pruritic nodules and contact allergy to aluminium after injection of commonly used aluminium-adsorbed vaccines

Rare cases of persistent pruritic nodules, sometimes associated with aluminium (Al) allergy, have been reported after the use of several Al adsorbed vaccines. During vaccine trials in the 1990s a high incidence of pruritic nodules (645 cases/76,000 recipients), in 77% associated with Al allergy, was observed after the administration of diphtheria–tetanus / acellular pertussis (DT/aP) vaccines from a single producer. In the present report 19 children with pruritic nodules after vaccination with Al hydroxide-adsorbed DTaP/polio+Hib (Infanrix, Pentavac) are described. The children had intensely itching nodules at the injection site, often aggravated during upper respiratory tract infections, and local skin alterations. So far, the symptoms have persisted for up to 7 years. The median time between vaccination and onset of symptoms was 1 month. 16 children were epicutaneously tested for Al, all with positive reactions indicating delayed hypersensitivity to Al. The condition is not commonly known but is important to recognise, as the child and the family may suffer considerably. Future vaccinations with Al-adsorbed vaccines may cause aggravation of the symptoms and the Al allergy. Al-containing skin products, such as antiperspirants, may cause contact dermatitis. Nodules may be mistaken for tumours. Even though the incidence of itching nodules and Al allergy after administration of Infanrix, Pentavac and other Al-adsorbed vaccines is probably low, research to replace Al adjuvants seems appropriate. We conclude that intensely itching subcutaneous nodules, lasting for many years, and hypersensitivity to aluminium may occur after DTaP/polio+Hib vaccination of infants.