LONDON SATURDAY JUNE 30 1951
THE PREVENTION OF WHOOPING-COUGH BY VACCINATION
A MEDICAL RESEARCH COUNCIL INVESTIGATION*
Since 1942 investigations have been in progress under the direction of the Whooping-cough Immunization Committee of the Medical Research Council to assess the prophylactic value of pertussis vaccines. From 1942 to 1944 controlled trials were made in Oxford City with children attending welfare clinics and day nurseries, and also in Oxfordshire, Berkshire, and Buckinghamshire with children in residential nurseries. A report of this work was published by McFarlan, Topley; and Fisher (1945). No significant difference was observed in the incidence or severity of the disease between the vaccinated and unvaccinated groups. In the Oxford City trial 12.5% of 327 vaccinated and 14.1% of 305 unvaccinated children developed pertussis, while in those residential nurseries in which whooping-cough occurred 55% of 33 vaccinated children and 63% of 30 unvaccinated children were attacked. Similar unfavour- able results have been reported by others. Doull and his colleagues (1939) described a trial, comprising 479 vaccinated and 496 unvaccinated children who were the older siblings of the former, in which the numbers of cases of pertussis in the two groups were 74 and 94 respectively. Siegel and Goldberger (1937), in a trial in a tuberculosis sanatorium, reported attack rates in children exposed to the disease of 53% in the vaccinated and 58% in the unvaccinated groups.
On the other hand, the majority of vaccination studies, most of which were made in the United States of America and Canada, indicated that pertussis vaccine produced a significant degree of protection. Many of these studies were reviewed by Felton and Willard (1944) and by Tudor Lewis (1946). The first hopeful results were observed by Zachariassen (see Madsen, 1933) in two epidemics in the Faroe Islands. A plain vaccine was used prepared from freshly isolated strains of Haemophilus pertussis. In the first epidemic, vaccination was begun during the outbreak and was found to have no effect on incidence, although it was reported to have reduced the severity of the disease. In the second epidemic, vaccination was completed shortly before the outbreak occurred, and of the 1,832 vaccinated children 75% contracted pertussis, compared with 98.2% among the 446 unvaccinated children. Encouraging results were later obtained by Sauer (1937), who used a plain vaccine prepared from strains which fulfilled the criteria for phase 1 H. pertussis described by Leslie and Gardner (1931). In this investigation Sauer vaccinated 1,122 children, and reported that of 128 who were subsequently exposed to pertussis, 94 in their own homes, only six developed the disease. Of the many studies made with plain vaccine the best known are those conducted by Kendrick and Eldering (1939). These studies comprised a total of 4,212 children, divided into vaccinated and unvaccinated groups which were similar in a number of respects. Of children exposed to infection in the home 34.9% in the vaccinated group contracted pertussis compared with 89.4% in the unvaccinated group.
In the majority of studies with plain vaccine the total dosage was relatively large in volume (sometimes 7 ml.) and in numbers of organisms (70 to 120 thousand million), and was given in three to five injections. More recently investigations have been made to determine whether effective protection could be obtained with alum-precipitated pertussis vaccine when given in smaller doses than those used with plain vaccines. Bell (1941, 1948) made two well-controlled trials, the first with alum- precipitated vaccine alone and the second with alum- precipitated combined pertussis vaccine and diphtherial toxoid. In each trial the total dose of vaccine was 20 thousand million organisms, given in two inoculations at an interval of four weeks. The incidence of the disease among the unvaccinated children was three to four times greater than that among the vaccinated. Kendrick (1942, 1943) also obtained good results with an alum- precipitated vaccine which was given in three doses.
In view of these favourable reports the Whooping- cough Immunization Committee concluded that the vaccines used in their trials in 1942-4 differed in some material though unknown way from those vaccines which had been shown to give protection. The Com- mittee therefore decided to carry out a new series of [end of text]
* The following collaborated in this investigation:
Members of the Whooping-cough Immunization Committee of the Medical Research Council: Professor S. P. Bedson, F.R.S. (chairman), Dr. W. C. Cockburn, Dr. E. T. Conybeare, Professor R. Cruickshank, Professor A. W. Downie, Professor A. Bradford Hill, Dr. P. L. Kendrick, Dr. J. Knowelden, Professor J. W. McLeod, F.R.S., Dr. H. J. Parish, Mr. A. F. B. Standfast, Dr. G. S. Wilson, Dr. D. G. Evans (secretary).
Medical Officers of Health: The late Dr. G. C. Williams (Oxford); Dr. C. Metcalfe Brown (Manchester); Dr. F. Roy Dennison (West Ham); Dr. G. Hamilton Hogben (Tottenham); the late Dr. A. G. Morison and Dr. E. Grundy (Wembley); Dr. J. Johnstone Jervis, Dr. J. F. Warin (Deputy M.O.H.), and Dr. I. G. Davies (Leeds); Dr. D. Regan (Edmonton).
Field Workers: Dr. M. Fisher and Miss C. Rudkin (Oxford): Dr. A. V. Magce and Miss O. I. Howell (Manchester); Dr. W. C. Cockburn, Miss M. A. Massey, and Miss M. M. Wall (Wembley, Tottenham, and Edmonton): Dr. G. R. Baxter and Mrs. E. R. Beard (Leeds); Dr. F. Barasi and Mrs. L. J. Bunch (West Ham).
Laboratory Workers: Dr. R. Knox (Oxford); Dr. H. W. Clegg, Dr. H. R. Cayton, and Dr. M. T. Parker (Manchester); Dr. A. J. H. Tomlinson and Dr. H. D. Holt (Colindale); Pro- fessor J. W. McLeod, Mrs. E. H. Farnworth, and Dr. B. Dawson (Leeds); Dr. W. W. Walther (West Ham).
The trials were planned with the advice of the Statistical Research Unit of the Medical Research Council and were arranged and supervised by Dr. W. C. Cockburn.
The results were analysed and the report prepared by Dr. W. C. Cockburn, Dr. D. G. Evans, and Dr. J. Knowelden.