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Annotations

IMMUNISATION AT SCHOOL ENTRY

AT present the Ministry of Health recommends thatchildren in this country be immunised against diphtheria,tetanus, and poliomyelitis before they enter school at fiveyears of age. For most of the children this would be areinforcement of artificial immunity established in infancy;but to some it will be necessary to give a primary course ofimmunisation. The requirements of the two groups aretherefore different.At the time of school entry it is convenient to try to fill

in the gaps in immunisation status. The importance ofdoing this for diphtheria has been repeatedly illustrated byschool outbreaks of the disease; and it is equally importantto cover tetanus and poliomyelitis immunisation at thistime. Children who need a primary course of immunisa-tion can be given two doses of adsorbed diphtheria andtetanus toxoids followed a year later by a booster dose.Protection against poliomyelitis can be provided by threedoses of attenuated trivalent oral poliovaccine. Immunisa-tion against these three diseases could also be achieved byuse of a combined poliomyelitis, diphtheria, and tetanusvaccine, which was shown to be satisfactory in six-month-old infants by Butler et al. 1

In our columns this week two schedules for reinforcingthe immunisation of schoolchildren against poliomyelitisare described. The paper by Dr. Beale and his colleagues(p. 879) discusses the efficacy of a single dose of attenuatedpoliovaccine at school entry. The results show that thegreat majority of children are immunised by this singledose whether it is given in drops or as a gelatin-coatedcapsule. The gelatin-coated capsule would be very usefulfor mass vaccination among adults, but it has no advantagefor school-entry children, and it is less satisfactory thanfluid vaccine for infant immunisation. When a single doseof attenuated poliovaccine is given, the adequacy of

immunity must depend on the number of children wholack antibodies to more than one type of poliovirus and onthe frequency of enterovirus excretion, which may inter-fere with the proper establishment of the vaccine virus.Beale et al. observed 7 children, out of 44 studied, inwhom immunity failed to develop, and they think that asecond dose of attenuated vaccine might be advisable forchildren at school entry. This opinion illustrates the highstandard of performance now expected of a vaccine.

Previously a vaccine inducing antibodies in 80% or morewould have been thought excellent.

Dr. Dane and his associates (p. 877), on the other

hand, studied the use of a combined diphtheria, tetanus,and inactivated poliovaccine of high potency. They foundthat all the children responded to poliovaccine, although(not surprisingly) only those who were receiving a re-inforcing dose responded to the diphtheria and tetanustoxoids. They conclude that the combined vaccine basedon inactivated poliovaccine is a satisfactory means ofreinforcing immunity at school entry, and that with theaddition of an adjuvant (for the toxoids) the vaccine wouldbe satisfactory for primary immunisation.

In both studies international units of poliovirus anti-body were used to express the results-the BritishStandard units used by Dane et al. are the same as theinternational units (the British Standard poliomyelitis

1. Butler, N. R., Wilson, B. D. R., Benson, P. F., Dudgeon, J. A., Ungar,J., Beale, A. J. Lancet, 1962, ii, 112.

antisera have been adopted internationally 2). The

serological results in the two investigations can thereforebe compared. The Belfast children were older andseemed to have higher titres before immunisation thanLondon children. In Belfast better results than wereobserved in London might possibly have been achievedby a single dose of attenuated poliovaccine, because verygood results were recorded 3 with a single dose of trivalentoral attenuated poliovaccine in schoolchildren some-

what similar in prevaccination antibody status to theBelfast children. Some failures must always be expectedwith a single dose of living vaccine, because of thehazard of interference from other viruses prevalent in thepopulation. As we have argued before, there seems to bemuch merit in the combined vaccine in simplifying theschedule of reinforcement of immunisation againstpoliomyelitis, diphtheria, and tetanus.None of the schedules we have mentioned have included

pertussis immunisation at school entry. There are two

opposing views about the best means of preventingwhooping-cough. Those who advocate early immunisa-tion do so because whooping-cough is severe and moreoften fatal in early infancy. Two objections are raised tothis view: immunisation must start very early, since it isin infants of less than three months that the disease is so

severe; and there are doubts about the efficacy of pertussisvaccine in such young children (the M.R.C. trial 4 wasconcerned with children over one year old). Butler et al.1,however, reported that the incidence of whooping-coughwas reduced by giving vaccine, starting at one week of age.But they relied on a questionary for their clinical follow-up.The other method of controlling whooping-cough in

young infants is by establishing a herd immunity: the aimis to achieve a high rate of pertussis immunisation, startingwith two primary doses after six months of age, followedby a booster dose at twelve to eighteen months and againat school entry. Difficulties have been raised here, too,since it has not been shown that a herd immunity can beestablished. Firstly, mild whooping-cough does some-times affect the immunised and may be a source of spread.Secondly, it may be doubted whether sufficiently highrates of complete immunisation can be attained to achievethe goal of a herd immunity. If pertussis immunisation isgiven at school entry, then a single dose of a combinedquadruple vaccine seems to be the simplest schedule, ortriple antigen with one or preferably two doses of attenu-ated poliovaccine. It can be argued that, since whooping-cough is not a serious hazard in schoolchildren, it is notjustifiable to give them another dose of a pertussis-contain-ing vaccine known to be associated sometimes withuntoward reactions, when the epidemiological advantagesare unproven.

IMMUNITY AND CYSTIC FIBROSIS

DURING the past ten years autoimmune antibodies to

many tissues have been found in various diseases. Targettissues include thyroid, kidney, connective tissue, uvealtract, red blood-cells, testis, and colon. Though thedetection of such antibodies does not prove that they causethe disease, there seems little doubt that some chronic orrecurrent diseases, such as disseminated lupus erythema-tosus, glomerulonephritis, or thyroiditis, are related toaltered or abnormal immune reactions.2. Lyng, J., Bentzon, M. W. Bull. Wld Hlth Org. 1963, 29, 711.3. Public Health Laboratory Service Report. Brit. med. J. 1962, ii, 142.4. Brit. med. J. 1957, ii, 1207.

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There is some evidence that patients with cysticfibrosis may be immunologically abnormal. Lowe andNeter 1 described a water-insoluble carbohydrate fractionfrom the mucoprotein in bile and other mucosal secretionsof patients with cystic fibrosis which could provoke pre-cipitins when injected into rabbits. Hennes et al. 2

observed that antibodies to human lung could be foundin the serum of patients with certain chronic destructivelung lesions. Thal and Murray 3 reported the presence ofantibodies to human pancreas in patients with cysticfibrosis. Talamo et al. now give a preliminary report ontheir search for such evidence. Studying urinary macro-molecules (e.g., glycoproteins, carbohydrates, and pro-teolytic substances), they could find no significant differencebetween cystic-fibrosis patients and the variablenormal pattern, except that transferrin was much reducedin cystic fibrosis. A more direct approach is that of Steinet al.5: using a gel-diffusion technique, they demonstratedspecific antibodies to cystic fibrotic lung and pancreas inthe bronchial mucus but not in the serum of cystic-fibrosis patients. Similar antibodies were not found incontrol patients with various diseases. (About half thosewhose bronchial mucus was examined appeared to havedestructive lung disease.) No antibodies to normal lungor pancreas were found.The significance of the presence of antibodies remains in

doubt. They may be merely the non-specific result oftissue destruction or they may be concerned in the pro-duction of some of the effects of cystic fibrosis. Muchwork may be needed before this doubt can be dispelled.

MYELOMATOUS OSTEOSCLEROSIS AND

PERIPHERAL NEUROPATHY

WHEN the nervous system is involved in myelomato-sis,6 -12 the lesions include compression of neural structuresby myeloma tissue or collapsed vertebrae, herpes zoster, 13-15amyloid infiltration of the carpal ligament,16 and amy-loidosis of the peripheral nervous system. 1 7 Snapperet al. 6 recognised in myeloma a form of peripheral neuritisin which no direct involvement of nerves or nerve-rootscan be demonstrated, and several other suggestive caseshave been reported, though pathological evidence, exceptthat supplied by Davison and Balser and by Scheinker,18was unconvincing.

In 1959 Victor et al. 19 reported 5 cases of multiplemyeloma with peripheral neuropathy. In 3 of them the

diagnosis was confirmed post mortem, and in 1 the

degeneration of the peripheral nerves was shown bybiopsy. In 2 of the cases examined post mortem theeffects of the neuropathy had dominated the clinical

1. Lowe, C. V., Neter, E. Amer. J. Dis. Child. 1957, 94, 400.2 Hennes, A. R., Moore, M. Z., Carpenter, R. L., Hammarsten, J. R.

Amer. Rev. resp. Dis. 1961, 83, 354.3. Thai, A., Murray, J. H. Ann. intern. Med. 1960, 53, 548.4. Talamo, R. C., Raunio, V., Gabriel, O., Pallavicini, J. C., Halbert, S.,

di Sant’Agnese, P. A. J. Pediat. 1965, 65, 480.5. Stein, A. A., Manlapas, F. C., Soike, K. F., Patterson, P. R. ibid.

p. 495.6. Snapper, I., Turner, L. B., Moscovitz, H. L. Multiple Myeloma.

New York, 1953.7. Geschickter, C. F., Copeland, M. M., Arch. Surg. 1928, 16, 807.8. Davison, C., Balser, B. H. ibid. 1937, 35, 913.9. Shenkin, H. A., Horn, R. C., Jr., Grant, F. C. ibid. 1945, 51, 125.

10. Bayrd, E. D., Heck, F. J. J. Amer. med. Ass. 1947, 133, 147.11. Clarke, E. Brit. J. Ophthal. 1953, 37, 543.12. Clarke, E. Brain. 1954, 77, 61.13. Anders, J. M., Boston, L. N. Lancet, 1903, i, 93.14. von Bomhard, H. Z. klin. Med. 1914, 80, 506.15. Wallgren, A. Upsala LäkFören. Förh. 1920, 25, 113.16. Grokoest, A. W., Demartini, F. E. J. Amer. med. Ass. 1954, 155, 635.17. Kernohan, J. W., Woltman, H. W. Arch. Neurol. Psychiat. 1942 47, 132.18. Scheinker, I. Dtsch. Z. Nervenheilk. 1938, 147, 247.19. Victor, M., Banker, B. O., Adams, R. A. J. Neurol. Neurosurg. Psychiat.

1958, 12, 73.

picture. In the first case there were sclerotic as well as

osteolytic foci in the femur, ischium, and sacrum; andthe lesion in the sacrum was shown by biopsy to be

myeloma. There had been only 1 previous report of

osteoplastic lesions in myeloma. 20 The protein in the

cerebrospinal fluid was increased in 4 of the cases ofVictor et al., even though there was no compression ofthe theca or its contents. Degeneration of the peripheralnerves was greatest distally, and the central chromatolysisin the anterior cells was judged to be retrograde degenera-tion. Myelin staining was pale in the posterior columnsin all three postmortem cases. Victor and his collaboratorswere only able to conclude that in both carcinomatousand myelomatous neuropathy some toxic or metabolic

abnormality was created in the peripheral nervous

system.Odelberg- Johnson 21 later reported a second case of

multiple myeloma with sclerotic changes in vertebra: andpelvic bones on radiological and postmortem examination.This patient had a typical picture of polyradicular neuritisten months before death, but no neuropathologicalexamination was carried out. Small et al .22 described athird case in which an apparently single sclerotic focusof myeloma (in the second lumbar vertebra) was associ-ated with a peripheral neuropathy with weakness at firstcorresponding to the level of the vertebra affected,though the absence of any thecal compression was shownfirst by operation and later at necropsy. The changesin the spinal cord were similar to those in Victor et al.’scases. Small 22 thought the changes in the intramuscularnerve-endings and muscle tissue suggested a con-

comitant myopathy (neuromyopathy), and he drewattention to the similar correspondence of the earlyparalytic symptoms with the level of the vertebral lesionin both his case and case 2 of Victor et al. He also

emphasised that the vertebral lesion in his case and Victoret al.’s case 1 was sclerotic.A fourth case has now been recorded by Aguayo et al. 23

The neuropathy began fourteen months before death,and at all times dominated the clinical picture andcaused death. The nerves of the limbs, trunk, andcranium were demyelinated, and again the posteriorcolumns degenerated. Aguayo et al. found 20 publishedcases of multiple myeloma with osteosclerotic lesions,and they mentioned a fifth case of sclerotic bone lesionsand neuropathy in myeloma which Brain had told themof. Aguayo et al. conclude that the association of periph-eral neuropathy and bone-forming lesions is a rare

finding and could possibly be only fortuitous, thougha common pathogenic factor may be responsible for bothlesions. Further observations are required to determinewhether the incidence of osteosclerotic lesions is reallygreater in myeloma with peripheral neuropathy than inother cases.

Sir CHARLES DoDDS has been re-elected president of theRoyal College of Physicians of London for the coming year.

Major-General L. T. PooLE, a former director of pathologyat the War Office, died at his home in Jedburgh on April 9.

Mr. L. R. BROSTER, consulting surgeon to Charing CrossHospital, died on April 12.

20. Krainin, P., D’Angio, C. J., Smelin, A. Arch. intern. Med. 1949, 84, 97621. Odelberg-Johnson, O. Acta radiol., Stockh. 1959, 52, 139.22 Small, J. M., Moxon, C. P., Woolf, A. L. Bgham med. Rev. 1961,

20, 546.23. Aguayo, A., Thompson, D. W., Humphrey, J. G. J Neurol. Neurosurg.

Psychiat 1964, 27, 562.