https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(97)11096-0.pdf

Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children

Bordetella respiratory infections are common in people (B. pertussis) and in animals (B. bronchiseptica). During the last two decades, much has been learned about the virulence determinants, pathogenesis, and immunity of Bordetella. Clinically, the full spectrum of disease due to B. pertussis infection is now understood, and infections in adolescents and adults are recognized as the reservoir for cyclic outbreaks of disease. DTaP vaccines, which are less reactogenic than DTP vaccines, are now in general use in many developed countries, and it is expected that the expansion of their use to adolescents and adults will have a significant impact on reducing pertussis and perhaps decrease the circulation of B. pertussis. Future studies should seek to determine the cause of the unique cough which is associated with Bordetella respiratory infections. It is also hoped that data gathered from molecular Bordetella research will lead to a new generation of DTaP vaccines which provide greater efficacy than is provided by today's vaccines.

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due to Bordetella pertussis and Other Bordetella Subspecies

Background Concern about both safety and efficacy has made the use of whole-cell pertussis vaccines controversial. In some European countries, including Italy, the rate of vaccination against pertussis is low. Methods We conducted a double-blind trial in Italy in which infants were randomly assigned to vaccination at two, four, and six months of age with an acellular pertussis vaccine together with diphtheria and tetanus toxoids (DTP); a DTP vaccine containing whole-cell pertussis (manufactured by Connaught Laboratories); or diphtheria and tetanus toxoids without pertussis (DT). The acellular DTP vaccine was either one containing filamentous hemagglutinin, pertactin, and pertussis toxin inactivated with formalin and glutaraldehyde (SmithKline Beecham) or one with filamentous hemagglutinin, pertactin, and genetically detoxified pertussis toxin (Chiron Biocine). Pertussis was defined as 21 days or more of paroxysmal cough, with infection confirmed by culture or serologic testing. Results The efficacy of eac...

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A Controlled Trial of Two Acellular Vaccines and One Whole-Cell Vaccine against Pertussis

The Vaccine Adverse Event Reporting System (VAERS).

Transposon Tn5 was used to isolate mutants of Bordetella pertussis. Strains with Tn5 insertions were screened for loss of virulence-associated factors, including filamentous hemagglutinin, hemolysin, and pertussis toxin. Several mutants deficient for hemolysin production were obtained. All produced dermonecrotic toxin, pertussis toxin, and filamentous hemagglutinin, but were found to vary with respect to adenylate cyclase production. One hemolysin mutant had no detectable adenylate cyclase activity; others had 0.6% or 16% wild-type activity, whereas a fourth seemed to be unaffected in terms of adenylate cyclase activity. Mutants deficient in the ability to hemagglutinate sheep erythrocytes were also isolated. These mutants either failed to synthesize or produced reduced amounts of three protein species of 200,000, 130,000, and 100,000 daltons, all of which reacted with antiserum to filamentous hemagglutinin. Pertussis toxin mutants were identified by screening culture supernatants for failure to induce a clustered growth pattern in Chinese hamster ovary cells, and identification was confirmed by the standard histamine-sensitizing assay in mice. These mutants will be useful to determine the relative contribution of each virulence factor to pathogenicity as well as to determine the identity of the antigens important in protective immunity.

https://iai.asm.org/content/iai/42/1/33.full.pdf

Tn5-induced mutations affecting virulence factors of Bordetella pertussis.

OBJECTIVE--To determine long term outcome in children who had a severe acute neurological illness in early childhood associated with pertussis immunisation. DESIGN--Follow up study of cases and matched controls. SETTING--Assessment of children at home and at school throughout Britain. SUBJECTS--Children recruited into the national childhood encephalopathy study in 1976-9 were followed up, with one of their two original matched controls, in 1986-9. MAIN OUTCOME MEASURES--Performance in educational attainment tests; behaviour problems reported by teachers and parents; continuing convulsions; evidence of other neurological or physical dysfunction. RESULTS--Over 80% of cases and controls were traced. Case children were significantly more likely than controls to have died or to have some form of educational, behavioural, neurological, or physical dysfunction a decade after their illness. The prevalence of one or more of these adverse outcomes in case children who had been immunised with diphtheria, tetanus, and pertussis vaccine within seven days before onset of their original illness was similar to that in case children who had not been immunised recently. The relative risk for recent diphtheria, tetanus, and pertussis immunisation in children who had died or had any dysfunction in comparison with controls was 5.5 (95% confidence interval 1.6 to 23.7). However, the number of cases associated with vaccine (12) was extremely small and statistically vulnerable, and other possible agents or predisposing factors could not be excluded. CONCLUSIONS--Diphtheria, tetanus, and pertussis vaccine may on rare occasions be associated with the development of severe acute neurological illnesses that can have serious sequelae. Some cases may occur by chance or have other causes. The role of pertussis vaccine as a prime or concomitant factor in the aetiology of these illnesses cannot be determined in any individual case. The balance of possible risk against known benefits from pertussis immunisation supports continued use of the vaccine.

https://www.bmj.com/content/bmj/282/6276/1595.full.pdf

Pertussis immunisation and serious acute neurological illness in children

There has been extensive debate in Great Britain regarding the risks and benefits of routine infant immunization against whooping cough. As a result of highly publicized cases of brain damage alleged to have been caused by the vaccine immunization acceptance rates have dropped dramatically and epidemics of the disease have recurred. On the basis of a review of the current state of knowledge on whooping cough the vaccine and vaccine safety the authors conclude that the dangers of the disease outweigh any known hazards of the vaccine. Although whooping cough is less important a cause of death and disability at present it remains a potentially lethal disease that should be controlled. The safety of the vaccine is an especially critical question however since it is being advocated for use on a mass scale in previously healthy children. The results of studies such as the National Childhood Encephalopathy Study suggest DPT vaccination is associated with a greater frequency of acute neurological illnesses than would be expected by chance. On the other hand most cases of such complications were not time-associated with DPT vaccination and may have resulted from the less purified vaccines used in the past. The most critical element in decision making is the readiness of parents and doctors to accept the fact that active preventive measures such as pertussis immunization sometimes carry unavoidable risks that have to be weighed against the risk of nonintervention.

Whooping cough and whooping cough vaccine: the risks and benefits debate

Measles vaccination and neurological events

Summary During the National Childhood Encephalopathy Study, standard neurodevelopmental assessments had to be performed on a large number of children under 3 years of age scattered throughout Great Britain. Currently available tests were reviewed but were found to be impractical for this purpose. We describe a simple test procedure, based on the STYCAR sequences, suitable for use in a clinic or at home with the minimum of special equipment. Results were reliable and provided an informative record of a child's developmental progress. It may be possible to modify the scheme for general use.

E. M. Ross

Papers

Pertussis immunisation and serious acute neurological illness in children

Whooping cough and whooping cough vaccine: the risks and benefits debate

Measles vaccination and neurological events

A developmental test based on the STYCAR sequences used in the National Childhood Encephalopathy Study