General BCG Vaccination of the Newborn as Safeguard Against Tuberculosis During Infancy

Summary In spite of the decrease in frequency, TB is still a folk‐disease in Sweden, We have no effective means of safeguarding against contracting TB when exposed to infection except preventive BCG vaccination. It has hitherto been supposed that no protective action sets in before a positive reaction to 1 mg Mantoux. According to earlier views, this takes at least six—eight weeks, while half of all those reacting later than this need up to about three—four months. Even where the inoculation takes, then, this period would be unprotected against infection. The possibility of warding off TB by the inoculation of all newborn infants depends to varying degrees on knowing that the risk exists. Such knowledge is essential during the first three months of life, and very important during the second and possibly even the third three months (= the UUprotected period + the incubation period of an infection contracted at the latest possible date during this vulnerable time), the point being that only newborn children known to be threatened by TB are isolated. However, in a recent inteiisive check‐up on expectant and recent mothers in Stockholm, G entz and B luhm found twice as many cases of unmistakably active TB in mothers as were previously known to exist. In a Stockholm material treated by J orup , children contracting TB during the first half year of life had practically without exception been infected by some member of the family. This state of affairs must be assumed to hold for the whole of Sweden. For this reason, a general BCG vaccination of all newborn children would not be much use without a more intensive check‐up on expectant and recent mothers. Such a check‐up is particularly necessary when delivery takes place at an institution, in view of the risk of infection to other mothers and children alike. According to G entz , nearly half of the young mothers in Stockholm at the beginning of the 1940's were themselves tuberculin negative. To this group of children should probably be added one at least as large, and very likely larger, where the fathers, inmates of the home, and other contacts had active TB eluding the present controls. The entire home surroundings should therefore be more carefully followed up. Facts are given, based on an investigation of the present author (1949) and on data from a work by J orup (1946), which suggest that the TB of the fathers is less widely known about than that of the mothers. Investigating TB in children under two years, J orup found the source of infection to be unknown in nearly 30 %, while in more than 30 % it came from older cases under observation, many of which had been diagnosed as not infectious, and in nearly 40 % the tubercle was discovered for the first time. Since, at the present time, isolation is only effected for those BCG‐vaccinated newborn children and infants known to be threatened by TB, and since the TB risk is often unsuspected, it means in point of fact that no isolation during the most dangerous period follows vaccination even for perhaps the majority of infants in the most threatened group, i.e. newborn children of tubercular mothers with definitely active TB. We might therefore expect to find that quite an appreciable number of BCG‐vaccinated children were infected before the vaccine took effect, and fell ill and died of TB. This does not seem to be the case, however. A survey by J orup of cases of children under two years treated for TB in children's hospitals in Stockholm during the years 1940–44 yielded only three BCG‐vaccinated children. and of these possibly only one who had been infected during the incubation period of the vaccine. Nowadays BCG vaccination is very common. In 1947, for example, half of all the children born in Stockholm were vaccinated at birth. In view of the results obtained by J orup and by G entz and B luhm , it seems hardly likely that almost all non‐isolated vaccinees should have escaped infection during these critical months. On the other hand, the total number of children in Jorup's material who contracted TR at an early age is surprisingly small when compared with the number of sources of infection cited by G entz and B luiim . It is therefore conceivable that some protection may start to form quite early in the incubation period of the vaccine, i.e. before the accepted standards of tuberculin positivity have been reached; and, similarly, that some protection still persists for a time after such positivity may have worn off; while, finally, even so‐called negative reactions may provide some safeguard. In support of this we advance the known fact that older inoculated areas may show a reaction on reinoculation of the subject dictated by failure to show tuberculin positivity; there is also an investigation by the present author (G yllensward 1949) which seems to demonstrate a reaction in the form of retarded increase in the weight of children vaccinated, as a rule, in the first three months of life. This retarding effect appeared no more than a few weeks after the inoculation ‐ that is to say, long before a positive reaction to even 1 mg Mantoux is customarily demonstrable. Reference is made to the significance of the general reaction when assessing states of immunity after inoculation against smallpox (G yllensward 1934 and 1936). The value of BCG vaccination, then, is greater than has been supposed. If inoculative protection begins to set in soon after inoculation and can be present even without a positive reaction to 1 mg Mantoux, and if it can be assumed to remain for some time after this reaction is no longer perceptible, this means correspondingly cheerful prospects that extensive BCG vaccinatioii of the newborn will be able to combat TB perhaps as early as the first and second three months of life — which prospects would look very gloomy if assessed on the findings of J orup , G entz and B luhm , and myself concerning the actual incidence of sources of infection and the chances of tracking them down. And the justifiability of an ‘emergency vaccination’ (W allgren ) gains further support. If the vaccine is already taking effect very shortly after administration, the question is raised, at any rate as regards cases where the prognosis is not very encouraging, whether it should not be considered normal, and not merely applicable to cases where satisfactory isolation froin the source of infection cannot be arranged, to vaccinate with BCG as soon as possible after infection has been suspected and/or a negative reaction established, without waiting for the end of the virulent infection's incubation period. Furthermore, it gives the neonatal period more to recommend itself as the correct age for a first general BCG inoculation than has hitherto been the case, quite apart from the purely practical consideration that it is so simple to get at newborn children who are born in an institution. As, however, the vaccinatioii seems to some extent to stop the children from putting on weight, premature and otherwise delicate newborn children should not he inoculated unless there is good reason for suspecting danger of T13. The same applies to the inoculation of delicate children and convalescents at later dates, and for the same reason concurrent inoculation of any other kind should be avoided. Furthermore, checking of a positive reaction should also be intensified, even though some inoculative protection is obtained before it sets in. The fact is that, in practice, there is no other method of making sure that some safeguard has been achieved, and the percentage of positive reactions to at least 1 mg Mantoux is cited in the reviewed surveys as varying from 80 % to only 50 % after vaccination of newborns. Résumé Jusqu'à présent on croyait que la vaccination ne confère pas cl'immunité avant l'apparition d'une intradermoréaction positive pour 1 mg de tuberculine. Si c'était réellement le cas, la vaccination par le BCG des nouveaux nés serait absolument incapable de fournir contre la tuberculose une protection plus grande, durant les trois à neuf premiers mois —éant donné l'apparition lente de la réaction — que celle apportée par l'isolement seul, loin des sources de contagion durant la période sans protection. Seuls les enfants que l'on sait exposés à la tuberculose sont isolés après la vaccination par le BCG. Des recherches indiquant qu'une tuberculose active mais ignorée est fréquente même chez les enfants allaites au sein maternel. L'auteur montre, cependant, qu'il y a probablement une réaction générale qui suit la vaccination par le BCG des nouveaux nés et apparaît sous forme d'un retard dans l'augmentation du poids. Elle se manifeste déjà quelques semaines après l'inoculation. Référence est donné a des recherches de l'auteur sur la significance d'une réaction générale suivant la vaccination contre la variole. Ainsi, il peut y avoir uiie immunité augmentant graduellement après la vaccination par le BCG, même avant 1'apparition d'une intradermoréaction positive pour 1 mg de tuberculine, et qui persiste quelque temps aprés que cette réaction positive a disparu. Il peut méme y avoir une certaine immunisation lorsque l'intradermoréaction avec 1 mg de tuberculine est restée negative. Cette hypothèse peut s'appuyer sur le fait qu'on trouve rarement des enfants vaccinés par le BCG parmi ceux qui contractèrent la tuberculose et en moururent. L'importance d'un retard pondéral comme contre indication à la vaccination BCG est discutée. Zusammenfassung Bisher hat man angenommen, dass die BCG‐Impfung keine Immunität gibt, solange die Tuberkulinreaktion für Mantoux (1 mg) nicht positiv ist. Wenn das wirklich der Fall wäre, so ist die BCG‐Impfung kaum mehr im Stande, in den ersten drei, ‐ wenn nicht sechs oder sogar neun Monaten, was auf der in vielen Fällen erst spät auftretenden Tuberkulinreaktion beruht ‐ gegen die Tuberkulose Schutz zu bieten, als es die einfache Isolierung von der Infektionsquelle tut. Isoliert werden nur solche Kinder, bei denen die drohende Ansteckungsgefahr bekannt ist. Man hat jedoch beobachtet und nachgewiesen, dass nicht erkannte aktive Tuberkulose bei den Müttern nicht selten vorkommt. Man sollte deshalb etliche Tuberkulosefälle bei BCG‐geimpften Kindern erwarten, die vor dem Tuberkulinumschlag der tuberkulösen Infektion ausgesetzt sind. Dies scheint jedoch nicht zuzutreffen. Der Verfasser zeigt, dass nach BCG‐Impfuiig im frühesten Säuglingsalter wahrscheinlich eine allgemeine Reaktion auftritt, welche sich in verlangsamter Gewichtszunahme äussert. Diese lässt sich schon einige Wochen nach der Impfung feststellen. Hierbei wird auf die Untersuchungen des Verfassers über die Allgemeinreaktion bei Erzielung der Pockenimmunität nach der Vaccination hingewiesen. Nach der BCG‐Impfung folgt also eine allmähliche Steigerung der Immunität, schon bevor die Mantoux‐reaktion für 1 mg positiv wird, wie auch eine gewisse Zeit nach dem Verschwinden der zuvor positiveii Mantouxreaktion noch eine gewisse Immunität bestehen bleibt. Es ist also möglich, dass nach der Impfung eine gewisse Immunität eintritt, auch wenn die gewöhnlich geforderte Tuberkulinempfindlichkeit nicht erreicht wird. Die Seltenheit der Todesfälle bei den BCG‐geimpften Kindern stützt die Richtigkeit der obengenannten Auffassung. Die Bedeutung der verlangsamten Gewichtszunahme als Kontraindikation gegen BCG‐Impfung wird diskutiert. Sumario Hasta ahora se ha creído yue la vacunación con BCG no produce inmunidad antes de la aparición de ma reacción positiva a 1 mg de tuberculina (Mantoux). Si esto es realmente así, la vacunación con BCG de los recién nacidos es enteramente incapaz de producir mayor protección contra la enfermedad tuberculosa. durante los tres primeros meses de vida — si no es de los seis o nueve primeros meses, debido, en muchos casos, a la reacción tardí— que la que se puede realizar por el simple aislamiento de las fuentes cle infección durante este período sin protección. Solamente los niños que están amenazados de contraer tuberculosis son aislados después de la vacunación con BCG. Se hace referencia a las investigaciones que han indicado que la tuberculosis activa, pero no reconocida, es frecueiite aún en las madres. El autor muestra, sin embargo, que hay probablemente una reacción general consecutiva a la vacunación que se manifiesta en la forma de un retardado aumento de peso. Esto puecle observarse a las pocas semanas de la inoculación. Se hace referencia a las investigaciones del autor sobre la significación de una reacción general después de la vacunación contra la viruela. De este modo puede producirse un aumeiito gradual de la inmunidad que sigue a la vacunación con BCG y aún antes yue 1 mg de tuberculina (Mantoux) produzca una reacción tuberculínica positiva y en este caso se mantiene lo mismo, por algún tiempo, después que la reacción positiva ha desaparecido. Puede haber aún alguna inmunidad que siga a la inoculación en la que la reacción tuberculínica, la naturaleza convencional de la cual está señalada, no ha sido alcanzada. Como soporte de esta suposición existe el hecho poco frecuente de que los niños calmetizados se encuentren entre los que han contraído y muerto por causa de la tuberculosis. Se discute la importancia que puede tener el retardado aumento de peso, como una contraindicación de la vacunación con BCG.