[A debate on pertussis vaccines. The monocomponent vaccine has many advantages].
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Biomedical subjects
Publications and source records attributed to B Trollfors.
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Two methods for determining the sensitivity of Haemophilus ducreyi to antimicrobial agents were compared; an agar dilution method and the Etest. The MICs of seven antimicrobial agents; penicillin V, ampicillin, trimethoprim, tetracycline, chloramphenicol, erythromycin and ciprofloxacin were determined for 20 strains of H. ducreyi. The MICs determined with the Etest and with the agar dilution method, showed 86% agreement within one two-fold dilution. The Etest is a good alternative method to the agar dilution technique for antimicrobial susceptibility testing of H. ducreyi. Owing to its simplicity and good reproducibility, the test is well suited for routine use in clinical microbiology laboratories in developing countries.
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The incidence, concomitant conditions and case fatality rate of Haemophilus influenzae (Hi) and pneumococcal meningitis and of invasive meningococcal infections were studied retrospectively in Sweden (population 8.4 million) for the years 1987-89, the period before vaccination against Hi type b started. A total of 1,019 cases with culture-verified infection were found. The incidence rates per 100,000 per year were 1.8 for Hi meningitis, 1.2 for pneumococcal meningitis and 1.0 for invasive meningococcal infections. The age-specific incidence was highest in the 3-23 months age group for the 3 bacterial species. Pneumococcal meningitis was common in individuals > or = 60 years and meningococcal infections in the age-group 10-24 years. A serious concomitant condition was known in 57% of all patients with pneumococcal meningitis while this was uncommon for the other organisms. The case fatality rate was 2% for Hi meningitis, 24% for pneumococcal meningitis and 10% for meningococcal infections. All 81 pneumococcal isolates which had been serotyped belonged to serotypes in the 23-valent pneumococcal vaccine. Of the meningococcal isolates, 65% belonged to serogroup B. In conclusion, the high incidence of Hib meningitis justifies general Hib vaccination. Development of a vaccine against N. meningitidis group B should have high priority. Furthermore, improved pneumococcal vaccines are needed for patients with predisposing conditions. The currently available pneumococcal polysaccharide vaccine seems to be underused.
A retrospective study of the incidence, aetiology and case fatality rate of acute epiglottitis in children and adults was performed. The study covered the whole of Sweden (population 8.4 million) during the years 1987-89, before general vaccination against Haemophilus influenzae (Hi) type b was started. Patients were included if it was documented that they fulfilled all 3 of the following criteria: (a) red and swollen epiglottis visualized by indirect laryngoscopy, (b) inspiratory stridor or difficulties in swallowing, and (c) a temperature > or = 38 degrees C. A total of 306 children and adolescents (0-19 years) and 502 adults (> or = 20 years) were found. The age-specific incidence was highest in children aged 0-4 years, (14.7/100,000 per year). The total incidence was 3.2/100,000 per year. In the age group 0-19 years, blood cultures had been obtained from 195 (64%) and Hi was isolated from 154 (79%). In adults (> or = 20 years), 114 of 298 blood cultures yielded Hi, while pneumococci were isolated from 5 and group A streptococci from 3 patients. A total of 220 children (72%) and 114 adults (23%) needed an artificial airway. Five children and 12 adults died. In conclusion, the incidence of acute epiglottis in Sweden is very high. Compared to a previous country-wide study covering the years 1981-83 that used the same methods for case finding and case definition, the incidence in children had decreased while the incidence in adults had increased.
BACKGROUND: Although many whole-cell vaccines have been effective in preventing pertussis, these vaccines are difficult to standardize and can produce side effects. In Sweden, pertussis became endemic during the 1970s despite vaccination. Because of its limited efficacy, the Swedish-made whole-cell vaccine was withdrawn in 1979. METHODS: To evaluate the efficacy of an acellular vaccine consisting of pertussis toxin inactivated by hydrogen peroxide (pertussis toxoid), we conducted a randomized, double-blind, placebo-controlled trial in Sweden. Infants were vaccinated with either diphtheria and tetanus toxoids alone (DT toxoids, 1726 infants) or diphtheria, tetanus, and pertussis toxoids (DTP toxoids, 1724 infants) at 3, 5, and 12 months of age. RESULTS: There were no serious reactions. With the pertussis vaccine there were slightly more local reactions than with the DT toxoids alone, but the rates of postvaccination fever were the same. The main period of surveillance, which began 30 days after the third vaccination, continued for a median of 17.5 months. There were 312 cases of pertussis (72 in the DTP-toxoids group and 240 in the DT-toxoids group) that met the clinical criterion (paroxysmal cough lasting > or = 21 days) and laboratory criteria for pertussis as defined by the World Health Organization. The efficacy of this acellular vaccine was 71 percent (95 percent confidence interval, 63 to 78 percent). The recipients of DTP toxoids who had pertussis had cough of shorter duration than the recipients of DT toxoids, and fewer had whooping and vomiting. The vaccine efficacy after two doses was 55 percent (95 percent confidence interval, 12 to 78 percent), on the basis of 14 cases in the DTP-toxoids group and 31 in the DT-toxoids group that met the definition of the World Health Organization. CONCLUSIONS: A pharmacologically inert, acellular pertussis-toxoid vaccine that is easily standardized is safe and confers substantial protection against pertussis.
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To study the specificity of serum antibodies against filamentous hemagglutinin (FHA) and pertactin for infection with Bordetella pertussis, we followed the acquisition of IgG serum antibodies against these 2 surface proteins of the organism in children who had been vaccinated with a monocomponent pertussis toxoid vaccine and who had experienced no symptoms of pertussis. Antibodies were estimated with enzyme-linked immunosorbent assay. In Part 1 of our study 5 consecutive samples obtained between 3 and 36 months of age from 71 children were available. Most had maternally derived antibodies to FHA (70 of 71) and pertactin (51 of 71) in the 3-month sera which declined in the subsequent sera. From about 1 year of age there were small but significant increases in antibodies against both antigens. At 3 years of age 71 of 71 had antibodies to FHA and 58 of 71 had antibodies to pertactin. In Part 2 of our study sera from 109 three-year old children were available. The 12 children with a history of family exposure to pertussis had significantly higher geometric mean titers of FHA antibodies than the 97 children with no history of family exposure. The geometric mean titers of pertactin antibodies did not differ. We suggest 3 explanations for the acquisition of FHA and pertactin antibodies in children with no history of pertussis: (1) asymptomatic B. pertussis infection in vaccinated children; (2) infection with Bordetella parapertussis; (3) infection with cross-reacting antigens from other organisms, e.g., nonencapsulated Haemophilus influenzae.
The serum IgG antibody response and decrease to 3 Bordetella pertussis antigens was compared in children with pertussis. Sera were obtained at the first clinical visit and 1, 3 and 12 months later from 89 children with > or = 3 weeks of paroxysmal cough. IgG antibodies to pertussis toxin (PT), to filamentous hemagglutinin (FHA) and to pertactin were determined with ELISA. Of 54 children with culture-confirmed pertussis or culture-confirmed familial exposure, 45 (83%) had a significant (> or = 3 fold) increase in PT IgG and 40 (74%) in FHA IgG antibodies, while only 29 (54%) had a significant increase in pertactin IgG antibodies. Significant decreases in PT, FHA and pertactin IgG antibodies were found in 34 (63%), 9 (17%) and 28 (52%) children, respectively. In the remaining 35 who did not have culture-confirmed disease, significant PT and/or FHA IgG antibody increases (criteria for pertussis according to the WHO definition) were found in 17 (49%). Only 6 of these 17 children had a significant pertactin IgG antibody increase. Of the remaining 18 children (who did not fulfil WHO criteria for pertussis), significant decreases in PT and/or FHA IgG antibodies were found in 13. We conclude that a serum IgG reaction to PT and FHA occurs in almost all children with pertussis. An increase in pertactin IgG antibodies occurs less frequently than against PT and FHA. Significant decreases in PT or FHA IgG antibodies in children with clinical pertussis might be of use as a diagnostic criterion in children brought late for examination.
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Antibodies against nonencapsulated Haemophilus influenzae and Moraxella (Branhamella) catarrhalis were measured by ELISA in paired sera from 158 adult patients with pneumonia. A mixture of 10 clinical isolates of each species was used as antigen. Eleven patients (7%) showed significant increases in antibody to H. influenzae. In 3 of them, the organism was isolated from transtracheal aspirate and in another 7 from sputum, nasopharynx, or both. Six patients with nonencapsulated H. influenzae in transtracheal aspirate cultures did not show any antibody increase. Six patients had significant increases in antibody to M. catarrhalis. The organism was isolated in transtracheal aspirates from 1 of them and in sputum and nasopharynx (or both) from another 3. Two patients with M. catarrhalis in transtracheal aspirate cultures showed no antibody response. In conclusion, the serologic methods increased the possibility to diagnose infections caused by the two agents but had low sensitivity.
One hundred forty-five infants were vaccinated with 25 micrograms of pertussis toxoid (NICHD-Ptxd) at 3, 5 and 7 or at 3, 5 and 12 months of age. One month after the third vaccination all had high serum IgG and neutralizing antibodies (antitoxin) against pertussis toxin. Vaccination at 3, 5 and 12 months resulted in higher antibody titers than vaccination at 3, 5 and 7 months. Sera obtained from 109 children at 3 years of age showed a decline of antibodies, but all had detectable antibodies. Adverse reactions were confined to local redness and swelling, which exceeded 2 cm after 17% of all injections. When the children were 3 years old, a comparison was made of the incidence of clinical pertussis in 142 of the 145 vaccinated children and in 284 age-matched controls living in the same areas. Information on symptoms of pertussis was obtained from the parents during telephone interviews. None of the vaccinated children had clinical pertussis, defined as a 6-week course of paroxysmal cough with whooping attacks or vomiting, whereas 57 controls (20%) had experienced these symptoms. Sixteen vaccinated children were exposed to pertussis in the household. Two of them had laboratory-verified Bordetella pertussis infections with cough of 2 and 4 weeks, respectively, without whooping attacks or vomiting, whereas 14 did not develop a cough. The study shows that NICHD-Ptxd is immunogenic in infants and that it most likely confers a high degree of protection against pertussis.
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A cost-benefit analysis of general vaccination of infants with a conjugated Haemophilus influenzae type b (HIB) vaccine was performed. Information on incidence and prognosis of HIB meningitis and acute epiglottitis in children was obtained from nation-wide retrospective studies covering the years 1981-83, when the birth rate was approximately 93,000 per year. The annual cost for hospitalization, neurologic and auditory sequelae and parents' absence from work amounted to 54 million Swedish crowns (SEK). A mean of 6 children died every year. Inclusion of value of lives lost added SEK 72 million to the cost of disease. With vaccine prices (approximately SEK 125/dose) and birth rate (approximately 120,000 per year) prevailing in 1993, vaccine costs would be SEK 45 million, provided that 3 doses are sufficient to offer protection close to 100%. Other costs for vaccination, e.g. physicians' and nurses' time, needles and syringes, are negligible, since the vaccine can be given at the same time as other infant vaccinations at already existing Child Health Centres. In conclusion, general vaccination of infants against HIB is cost-effective, saves lives and reduces human suffering.
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In Sweden general vaccination with a whole cell pertussis vaccine was recommended from 1953. In 1979 the recommendation was withdrawn because the Swedish-made vaccine had become ineffective. In order to determine the incidence of the disease in a nonvaccinating country, 400 children born in 1980 were randomly selected from the population register of Göteborg, Sweden. The parents of the children were interviewed in 1990, when the children were 10 years old. The parents of 377 children could be reached, and of those 372 were not vaccinated against pertussis. Of the nonvaccinated children 61% had experienced clinically typical whooping cough; 195 (119 with and 76 without a history of whooping cough) agreed to donate a serum sample for determination of antibodies against pertussis toxin, filamentous hemagglutinin and pertactin. Of the children with a history of whooping cough, 91% had antibodies against pertussis toxin, as had 64% of the children without a history of disease. All but 3 children had antibodies against filamentous hemagglutinin and all 195 children had antibodies against pertactin. The antibody titers against the 2 last mentioned proteins did not differ between children with and without a history of whooping cough or between children with and without antibodies against pertussis toxin.