pertussis prophylaxis

2
486 and Captain FEASBY, who report in this issue the combination of Raynaud’s syndrome and autoagglu- tination, regard them both as caused by chilling in a cold-sensitive patient. The blood of outwardly normal people may also show it; an example is provided on another page by Dr. PARISH and Dr. MACFARLANE’S report of an unusual case in which ionised calcium played a part, and it is noteworthy that, though their patient was an allergic subject with angioneurotic oedema, the autoagglutination was not connected with any allergic attacks. Autoagglutination is not com- mon, but among the large numbers of people now being grouped by the transfusion services some are bound to show it, and- since the ordinary grouping tests will not detect them the effects of possible mis- grouping are worth examination. 0 When blood is taken for the grouping test sufficient plasma is carried over to agglutinate the red cells even in the presence of test sera ; the autoagglutinator will therefore be recorded as group AB when in fact he might be any of the other groups. If his blood is taken for transfusing a group AB patient unexpected agglutination will take place when his cells are tested against the patient’s serum. The next step is usually to try another specimen of blood, so that as long as cross-matching is possible no harm will be done, and in emergencies when time does not permit cross- matching group 0 blood-never group AB-is used. If the autoagglutinator’s blood is turned into serum or plasma the results are again unlikely to be serious I since the abnormal agglutinin is usually inactive at 37° C., and with the large batches of pooled plasma now used the abnormal agglutinin will be much diluted. The true group of an autoagglutinator can usually be determined by repeating the tests at 37° C. or by washing the red cells in saline before testing. If the incorrectly grouped autoagglutinator is himself to receive blood he will be safe so long as cross-matching is properly done, when unexpected agglutination should indicate the necessity for repeating the group- ing test at 37° C. The drip method is undoubtedly the safest way of giving blood to such a patient. The mass-production tactics of the transfusion services make it difficult for every group AB donor to be regrouped using precautions to detect autoagglutina- tors, and such regrouping is not vital. On the other hand, when patients in need of transfusion for severe anaemia are found to be group AB, it is worth while to exclude autoagglutination. The second problem, involving group-specific iso- agglutinins, arises in connexion with the use of serum for transfusion. Just as the blood-banks store group 0 blood for emergency use because its red cells contain no agglutinogens, so from a theoretical standpoint , group AB serum is the ideal since it contains no agglutinins. But only 3-7% of donors are group AB ; much of the plasma and serum comes necessarily from the 40-46% of donors who are group 0 and therefore contains both anti-A and anti-B agglutinins. BRYCE and JAKOBOWICZ/ who made a quantitative examination of a large number of group 0 sera, found that 3l’2% had an anti-A titre and 10-1% an anti-B titre of over 1 in 100. It is generally thought desir- able that plasma or serum, especially concentrated serum, should be freed from these isoagglutinins, and the fact that it is more difficult for serum to be so 1. Bryce, L. M. and Jakobowicz, R. Med. J. Aust. 1941, 1, 290. freed has been made a point against its use. Mixing of group A and group B blood before separating the plasma, so that the A cells absorb the anti-A iso- agglutinins of group B blood and vice versa, has been one method, but this again limits the donors to about 50% of those available. DELLA VIDA and DYKE 2 utilised the fact that agglutinogens are not limited to the red blood-cells but also occur in body fluids includ- ing plasma and serum, so that group A serum can be used to absorb the anti-A isoagglutinins of group B serum and vice versa. They showed how with group 0 serum the agglutinin titre could be considerably reduced, even if not completely absorbed, by mixing in suitable proportions with group A and B sera, so that the blood of all groups could be used. A third method is suggested by WITEBSKY, KLENDSHOJ and SWANSON.3 They point out that the group-specific substances (agglutinogens) are complex carbohydrate- like bodies resembling the capsular substance of pneumococci. Group A substance can be prepared from commercial pepsin, mucin or peptone, but group B substance has so far only been isolated from the gastric juice of group B persons. By adding these two group-specific substances to group 0 blood they are able to reduce the titre of the anti-A and anti-B agglutinins in the plasma to a safe level. This method is an interesting application of our increasing know- legdge of the nature of the blood groups but is hardly suitable as yet for large-scale work. Clinical reports of reactions after the transfusion of group 0 serum into patients of other groups are scanty, and it is not yet clear how far the presence of anti-A and anti-B isoagglutinins is really detrimental. The definition of safe limits for the titres of these agglutinins in pooled serum should not be too difficult and would provide the transfusion services with a useful standard. PERTUSSIS PROPHYLAXIS THE present prevalence of whooping-cough reminds us how little has been attempted in this country towards the prevention of this preventable disease. Too many of us still regard pertussis and measles as the inescapable and not very serious afflictions of childhood. But in London these two rank fourth and fifth among the causes of death in children under five years, and in hospital practice the case-fatality from pertussis exceeds that of both measles and diphtheria (L.C.C. Annual Report, 1935). Moreover, about a tenth of the cases and two-fifths of the deaths from pertussis occur in the first year of life 4 while STOCKS estimated that 44% of London children developed the disease before their fifth birthday. Prophylaxis of so prevalent a respiratory infection could only be possible by specific vaccination, and this method of prevention has been shown, particularly in America, to be a practical possibility. Unfortunately, four or five weekly injections of large doses (10-30 thousand million organisms) of a carefully prepared smooth- phase vaccine are apparently necessary to secure an effective immunity, which for large-scale immunisa. tion introduces serious problems in production and administration. The possibility of protecting the child by fewer doses of the vaccine spaced at longer intervals, as has been proved effective with diphtheria 2. Della Vida, B. L. and Dyke, S. C. Lancet, 1941, 1, 564. 3. Witebsky, E., Klendshoj, N. C. and Swanson, P. J. Amer. med. Ass. 1941, 116, 2654. 4. Zamkin, H. O. Amer. J. publ. Hlth, 1940, 30, 394.

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Page 1: PERTUSSIS PROPHYLAXIS

486

and Captain FEASBY, who report in this issue thecombination of Raynaud’s syndrome and autoagglu-tination, regard them both as caused by chilling in acold-sensitive patient. The blood of outwardly normalpeople may also show it; an example is provided onanother page by Dr. PARISH and Dr. MACFARLANE’Sreport of an unusual case in which ionised calciumplayed a part, and it is noteworthy that, though theirpatient was an allergic subject with angioneuroticoedema, the autoagglutination was not connected withany allergic attacks. Autoagglutination is not com-mon, but among the large numbers of people nowbeing grouped by the transfusion services some arebound to show it, and- since the ordinary groupingtests will not detect them the effects of possible mis-grouping are worth examination.

0

When blood is taken for the grouping test sufficientplasma is carried over to agglutinate the red cellseven in the presence of test sera ; the autoagglutinatorwill therefore be recorded as group AB when in facthe might be any of the other groups. If his blood istaken for transfusing a group AB patient unexpectedagglutination will take place when his cells are testedagainst the patient’s serum. The next step is usuallyto try another specimen of blood, so that as long ascross-matching is possible no harm will be done, andin emergencies when time does not permit cross-

matching group 0 blood-never group AB-is used.If the autoagglutinator’s blood is turned into serumor plasma the results are again unlikely to be serious

I since the abnormal agglutinin is usually inactive at37° C., and with the large batches of pooled plasmanow used the abnormal agglutinin will be muchdiluted. The true group of an autoagglutinator canusually be determined by repeating the tests at 37° C.or by washing the red cells in saline before testing. Ifthe incorrectly grouped autoagglutinator is himself toreceive blood he will be safe so long as cross-matchingis properly done, when unexpected agglutinationshould indicate the necessity for repeating the group-ing test at 37° C. The drip method is undoubtedlythe safest way of giving blood to such a patient.The mass-production tactics of the transfusion servicesmake it difficult for every group AB donor to be

regrouped using precautions to detect autoagglutina-tors, and such regrouping is not vital. On the otherhand, when patients in need of transfusion for severeanaemia are found to be group AB, it is worth whileto exclude autoagglutination.The second problem, involving group-specific iso-

agglutinins, arises in connexion with the use of serumfor transfusion. Just as the blood-banks store group0 blood for emergency use because its red cells containno agglutinogens, so from a theoretical standpoint

, group AB serum is the ideal since it contains no

agglutinins. But only 3-7% of donors are groupAB ; much of the plasma and serum comes necessarilyfrom the 40-46% of donors who are group 0 andtherefore contains both anti-A and anti-B agglutinins.BRYCE and JAKOBOWICZ/ who made a quantitativeexamination of a large number of group 0 sera, foundthat 3l’2% had an anti-A titre and 10-1% an anti-Btitre of over 1 in 100. It is generally thought desir-able that plasma or serum, especially concentratedserum, should be freed from these isoagglutinins, andthe fact that it is more difficult for serum to be so

1. Bryce, L. M. and Jakobowicz, R. Med. J. Aust. 1941, 1, 290.

freed has been made a point against its use. Mixingof group A and group B blood before separating theplasma, so that the A cells absorb the anti-A iso-agglutinins of group B blood and vice versa, has beenone method, but this again limits the donors to about50% of those available. DELLA VIDA and DYKE 2

utilised the fact that agglutinogens are not limited tothe red blood-cells but also occur in body fluids includ-ing plasma and serum, so that group A serum can beused to absorb the anti-A isoagglutinins of group Bserum and vice versa. They showed how with group0 serum the agglutinin titre could be considerablyreduced, even if not completely absorbed, by mixingin suitable proportions with group A and B sera, sothat the blood of all groups could be used. A thirdmethod is suggested by WITEBSKY, KLENDSHOJ andSWANSON.3 They point out that the group-specificsubstances (agglutinogens) are complex carbohydrate-like bodies resembling the capsular substance ofpneumococci. Group A substance can be preparedfrom commercial pepsin, mucin or peptone, butgroup B substance has so far only been isolated fromthe gastric juice of group B persons. By adding thesetwo group-specific substances to group 0 blood theyare able to reduce the titre of the anti-A and anti-Bagglutinins in the plasma to a safe level. This methodis an interesting application of our increasing know-legdge of the nature of the blood groups but is hardlysuitable as yet for large-scale work. Clinical reportsof reactions after the transfusion of group 0 seruminto patients of other groups are scanty, and it is notyet clear how far the presence of anti-A and anti-Bisoagglutinins is really detrimental. The definitionof safe limits for the titres of these agglutinins inpooled serum should not be too difficult and wouldprovide the transfusion services with a useful standard.

PERTUSSIS PROPHYLAXISTHE present prevalence of whooping-cough reminds

us how little has been attempted in this countrytowards the prevention of this preventable disease.Too many of us still regard pertussis and measles asthe inescapable and not very serious afflictions ofchildhood. But in London these two rank fourth andfifth among the causes of death in children under five

years, and in hospital practice the case-fatality frompertussis exceeds that of both measles and diphtheria(L.C.C. Annual Report, 1935). Moreover, about atenth of the cases and two-fifths of the deaths from

pertussis occur in the first year of life 4 while STOCKSestimated that 44% of London children developed thedisease before their fifth birthday. Prophylaxisof so prevalent a respiratory infection could only bepossible by specific vaccination, and this method ofprevention has been shown, particularly in America,to be a practical possibility. Unfortunately, four orfive weekly injections of large doses (10-30 thousandmillion organisms) of a carefully prepared smooth-phase vaccine are apparently necessary to secure aneffective immunity, which for large-scale immunisa.tion introduces serious problems in production andadministration. The possibility of protecting thechild by fewer doses of the vaccine spaced at longerintervals, as has been proved effective with diphtheria2. Della Vida, B. L. and Dyke, S. C. Lancet, 1941, 1, 564.3. Witebsky, E., Klendshoj, N. C. and Swanson, P. J. Amer. med.

Ass. 1941, 116, 2654.4. Zamkin, H. O. Amer. J. publ. Hlth, 1940, 30, 394.

Page 2: PERTUSSIS PROPHYLAXIS

487

toxoid, had not until recently been given a serioustrial under controlled conditions. McLEAN 5 at aclinic at St. Mary’s Hospital vaccinated 513 childrenover a period of 4 years, using three doses of 4000million organisms at 3-7 day intervals followed by afourth dose a month later, and he reported no cases ofwhooping-cough among 46 known and 45 suspectedexposures, whereas in a control group of 154 children,89 cases followed 115 exposures. ScHUTZB*’ 6 showed

experimentally that the combination of diphtheriaalum-precipitated toxoid and pertussis vaccine had noinhibitory action on the immunising property ofeither antigen, and the idea of combined immunisa-tion against these two diseases has been gainingground. A single dose of an alum-precipitatedpertussis vaccine was given a clinical trial in Maryland,U.S.A., in 1936-37, and although the evidence of

protection was not such as to justify recommendationof the " one-shot " vaccine there were no severereactions.A large-scale investigation in Norfolk, Virginia, was

therefore planned to find if two doses of the alum-precipitated vaccine at a month’s interval would givereal protection against pertussis. The first report 7on this investigation is largely concerned with theplanning of the experiment so as to obtain (1) aninjected group identical in all essentials with a controluninjected group, (2) the uniform observation of bothgroups over an adequate period of time, and (3) adefinition of pertussis as a clinical entity which couldbe uniformly recognised. The difficulties encoun-

tered need not be enumerated ; the manner in whichthey were tackled and largely overcome should becarefully studied by any team of workers likely toundertake similar field studies in this country. Two1 c.cm. doses of an alum-precipitated vaccine con-taining 10,000 million organisms - per c.cm. were

injected subcutaneously in the deltoid region of firstone arm and then the other at a month’s interval.Very few children had any systemic reaction ; therewas some local tenderness and stiffness, but if thevaccine was not injected too superficially the firmnodule which usually developed was not noticed bythe parents. After various discards there remainedfor analysis 641 vaccinated (V) and 571 non-vaccinated(N) children, and these were divided into two age-groups according as they were born (A) before and (B)after July 1, 1937. The table, taken from a larger

table illustrating the comparative incidence of measles,chickenpox and mumps in the two groups, shows theincidence of pertussis in vaccinated and unvaccinatedchildren before June 1, 1938, when vaccination was

begun, and for 34 months after that date. The

5. McLean, I. H. Proc. R. Soc. Med. 1940, 33, 425.6. Schütze, H. Lancet, 1940, 2, 192.7. Bell, J. A. Publ. Hlth Rep., Wash. 1941, 56, 1535.

results are not very different from those obtainedin their large-scale and carefully controlled experi-ment by KENDRICK and ELDERLING 8 who used a totalof 70,000 million organisms given in four weekly doses,and reported an annual attack-rate of 2-3% in theinoculated and 15-1% in the controls. As usuallyhappens, it was noted in the Virginia series that

pertussis when it did occur in a vaccinated child wasmilder and of shorter duration than the attack in theuninoculated children. These results with alum-precipitated pertussis vaccine should encourage healthauthorities to combine the pertussis vaccine withdiphtheria A.P.T., in which case it would seem

advisable to start the double immunisation during thesecond six months of life, for at that age pertussistakes a heavy toll of infected children.

Passive protection against the infection by the useof human blood or serum has been claimed to beeffective (MEADER).9 Using the method of intranasalinfection of mice, NORTH and others 10 found that theserum of child convalescents or of immunised children

protected against large infecting doses, whereas pooledadult serum protected only irregularly againstsublethal mouse infections. Fortunately pertussishas not the high infectivity of measles or chickenpoxwhen it is introduced into a hospital ward, so that theneed for passive protection is less urgent. But in thehome any child under two years who has been exposedto infection might with advantage be given a pro-tective dose of human serum. For this purpose panelsof immunised donors could with a little organisationbe made available.

Annotations

THE HEN AS MIDDLEMAN

FOB years we have been taught that as a middlemanbetween vegetable products (particularly grain " offals ")and human food the hen, of aJl domestic animals, is themost wasteful and the cow the least. Some publicistseven went so far as to give figures for the relative meritof cow, pig, bullock and hen ; and the hen, as converterof fodder into food, was invariably placed last. Thecow was reckoned to be five times as efficient as the henand the pig ranked next to the cow. Thus it was con-sidered uneconomical to use offals in producing beef,eggs and fowls (roasters and boilers), and the Govern.ment gave priority in feeding stuffs to dairy cows, bothin the war of. 1914-18 and in the present war, and ratedhens last. It is not clear whether these assessmentswere based on the total dry constituents produced from(say) 100 lb. of fodder, or on the calories or the protein ;and it is essential in assessing the efficiency of cow andhen that we should know what we are aiming at. It is

possible, and indeed likely, that the order of meritwould need revision if we considered the protein deriv-able by hen power from a given weight of fodder protein.This is clear from a recent article by E. T. Halnan 11of the Animal Nutrition Institute at Cambridge.Halnan, being an authority on poultry, naturallydefends the animal of his choice from the obloquycast on it by agriculturists and dietitians. It seemsthat she has been maligned as a manufacturer of first.class protein from the proteins of lower biological valuein offals. According to Halnan’s estimates the henconverts 100 lb. of digestible fodder protein into 31-6 lb.

8. Kendrick, P. and Elderling, G. Amer. J. Hyg. 1939, 29, 133.9. Meader, F. H. Amer. J. Dis. Child. 1937, 53, 760.

10. North, E. A., Keogh, E. V., Anderson, G. and Williams, S.Aust. J. exp. Biol. med. Sci. 1939, 17, 275; North andAnderson, Med. J. Aust. 1941, 1, 754.

11. Nature, Lond, 1941, 148, 335.