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VACCINATION AGAINST MEASLES
728
VACCINATION AGAINST MEASLES
diverse routes-by intranasal instillation, 1 c.cm. into each nostril ; by inhalation, 1 c.cm. atomised DESPITE early success against smallpox and rabies directly beneath the nose into a cellophane" shower active immunisation against virus infections has in cap " covering the child’s head, making a barely general been slow and beset with difficulties. Even visible fog containing no large droplets ; by the against influenza and poliomyelitis, on both of subcutaneous route alone or combined with the nasal which much study has been concentrated, the progress route ; and by intradermal injection, 0’2-1 c.cm. of achieved has disappointed early hopes. In the light 1 in 10 to 1 in 10,000 dilutions according to the of these experiences the recent attempts to confer number of egg passages. Finally, upwards of 27 immunity against measles by means of attenuated groups of children comprising the vaccination experi. virus vaccination must be studied critically. Nor ments were subdivided into two groups of presumed should the previous work on measles itself be forthose had been under constant who susceptibles ; (a) gotten. In 1759 HOME1 claimed to have protected medical supervision from birth, and (b) those not susceptibles against attack by scarifying them with so well looked after, in whom an attack of measles assumedly infective blood taken from patients who have been overlooked or forgotten. Measles had recently had measles, but subsequent workers might of varying severity followed inoculation in 74% of could not confirm this observation. HERMANN2 in the 255 children inoculated, and if 32 doubtful cases 1914 instilled filtered nasopharyngeal washings into are included the figure rose to 92%. The incubation the anterior nares of babies 3-5 months old in order was period usually shorter (6-7 days) than in natural to raise and perpetuate the passive immunity they but occasionally it was prolonged. The measles, are assumed to derive from their mothers, but the observers were impressed by the paucity and mildmethod was soon abandoned because unmodified ness of symptoms, especially the almost complete attacks were too frequent and dangerous to be absence of cough, although the rash was sometimes disregarded. HIRARSHI and OKAMOTA3 in 1921, brilliant and the temperature high but transient. and later DEBBE and his associates,4 claimed to have As regards efficacy of route, intranasal drip returned induced by the inoculation of various dilutions of only 30% positive " takes," compared with 80% blood from measles patients attenuated attacks after intradermal injection and 98% with the inhaled conferring an immunity sufficient to render the spray. Of 35 presumed non-immunes who were inoculated insusceptible to further injections. Apart regarded as unsuitable for vaccination but were from their inherent risk these experiments were exposed to subjects with an attenuated attack, necessarily limited in scope and application since 16 showed no response, 6 were doubtful and 13 had fresh blood had to be used for each inoculation. For attacks similar to those in the inoculated-in other 20 years the limited success which has attended the words, there was no reversion to unattenuated or use of immune measles serum (convalescent, placental normal measles, at least by one human passage. and normal adult) in the prevention and modification A reporton 22 children observed for a year after of measles has diverted the attention of workers in successful vaccination shows that, after chance this field from active prophylactic methods, but in exposure, 15 did not contract measles, 3 had unmodithe last 5 years the researches of PLOTZin France fied attacks, 1 had an extremely mild attack and in and of STOKES and RAKE 6 in America on the 3 the disease was so mild as to be identified with cultivation of measles virus on the chorioallantoic difficulty. An illustration of the protection afforded membrane of the developing chick embryo, and their was given by a group of 7 vaccinated children who demonstration of attenuation of the virus by repeated escaped entirely, in contrast to 25 attacks among egg-passages, first on monkeys and later on sus- 36 unvaccinated but otherwise similar children ceptible humans, has raised hopes that a practicable exposed in the same school. An additional 24 method of active immunisation has at last been children of the vaccinated group were given challenge discovered. of blood taken from active cases of measles ; injections The new antigen has been tried in Philadelphia in in 13 no disease followed, in 3 there was typical collaboration with field workers.’ Although egg- measles, in 2 mild attacks and in 5 mild extremely passage attenuated virus had previously been attacks ; 6 unvaccinated children given similar assayed on monkeys (Maccacus mulatta is a convenient challenge injections all developed typical unmodified animal and uniformly susceptible) the conditions of measles. RAKE 9 reports on two further trials the experiments now recorded were altered so fre- conducted since July, 1943, for the board investiquently that often there were insufficient numbers gating epidemic diseases in the Army. In Baltimore in a particular group of trials for the validity of the 827 coloured children assumed to be susceptible findings to be assessed. Virus of from 3 to 66 serial from the parents’ history were vaccinated ; of 412 passages was used in different experiments, the 26th of these who were carefully followed up, 145, or to 40th passage-virus being most constant in effect. 35%,’showed definite signs of mild measles. The The material was either kept frozen at -35° C. and number may have been greater, for a faint rash is thawed immediately before inoculation, or was readily overlooked in negroes. In Philadelphia 199 desiccated from the frozen state and reconstituted white children who had never had measles according to its original volume ; this procedure did not demonto their physicians’ records were vaccinated, and 172 strably alter activity. Inoculations were given by followed up ; of these, 131, or 76%, gave an equally 1. Home, F. Medical Facts and Experiments, London, 1759, p. 253. satisfactory response, the higher percentage being 2. Hermann, C. Arch. Pediat. 1914, 31, 885. ascribed to the more accurate history. 3. Hirarshi, S. and Okamota, K. Jap. med. World, 1921, 1, 10. 4. Debré, R. and Ravina, A. Bull. Soc. méd. Hôp. Paris, 1923, Summing the vaccinations to date, 1281 children 46, 226. have been inoculated without untoward effect; 5. Plotz, H. Bull. Acad. Méd. Paris, 1938, 119, 598.
VACCINATION AGAINST MEASLES
’
6. Stokes, J. and Rake, G. Science, 1940, 92, suppl. p. 10. 7. Stokes J., O’Neil, G. C., Shaffer, M. F., Rake, G. and Maris, E. P. J. Pediat. 1943, 22, 1.
Rake, G., Stokes, J., Shaffer, M. F. and O’Neil, 9. Rake, G. Ibid, 1943, 23, 376. Ibid, p. 17.
8. Maris, P.,
G. C.
729
TRIPLE RHYTHM
839 of them were carefully investigated revealing that 450 (54%) had definite evidence of modified measles. The absence of a clinical or serological test of immunity is a serious but not crucial handicap in assessing the efficacy of the measure. The sample of 40 proved protected out of 46 at intimate risk is impressive but not conclusive, since natural immunity remains a possibility ; an extended trial under ex. acting conditions should certainly be made, especially as the method has the virtue of being innocuous.
TRIPLE RHYTHM WORK done at oir JAMES MACKENZIEold departHospital goes far to explain the
ment at the London
significance of triple heart rhythm-‘the cadence produced when three sounds recur in successive cardiac cycles," as Evgrrs defines it in his Strickland Goodall lectured He has studied by phonocardiography the heart sounds in 270 patients over the age
,
of 9 years who were either known to have heart disease or were sent to his department for an opinion on their heart, and were found on auscultation to have triple rhythm.. No phonocardiogram was taken unless triple rhythm was first detected by the stethoscope, and his survey does not deal with splitting of the first sound at the apex or of the second at the base of the heart. He now suggests that terms like " gallop rhythm " should be discarded, and that we should speak of three types of triple rhythm. In type 1 the added sound is found early in diastole, immediately after the second sound (lub dupty-); it is the third sound of the normal cardiac cycle. In type 2 the extra sound comes late in diastole (tylub dup-) and corresponds to the fourth sound of the cardiac cycle. In type 3 it comes towards the end of systole, just before the second heart sound (lub tydup-). Types 1 and 2 are each divided into two subgroups. There were 205 patients with triple rhythm type 1, of whom 125 seemed healthy (la) and 80 had evidence of some form of heart disease (lb). The healthy ones were mostly young people, none being over 40, and it may be recalled that MANNHEIMFR2 found a third heart sound by phonocardiography in 70% of healthy These patients’ extra sound was best children. heard midway between the nipple line and the lateral border of the sternum, and was accentuated when the pulse was quickened or the patient lay down. In agreement with BRAMWELL’s observationcardioscopy showed a prominent pulmonary artery in most of these patients-47 out of 50 consecutive patients showed such a prominence, compared with 7 out of 50 controls of the same age-group with dual rhythm. In type 1b the extra sound was best heard in the mitral area or external to it, and it could usually be heard with the patient sitting up as well as lying down. It occurred in older patients than type la and was associated with lesions that produce enlargement and failure of the right side of the heart, such as
mitral stenosis, hypertension, thyrotoxicosis,
congenital heart disease, emphysema and pulmonary hypertension. In mitral stenosis the triple rhythm was commoner
with auricular fibrillation than with
rhythm, and its presence pointed to considerable enlargement of the right side of the heart. In hypersinus
1. Evans, W. Brit. Heart J. 1943, 5, 205. 2. Mannheimer, E. Acta pœdiatr., Stockh. 1940,
Lancet, 1941, i, 607).
28, suppl. 2 (see
3. Bramwell, C. Brit. Heart J. 1943, 5, 24 (see Lancet, 1943, ii,
279).
tension this type of rhythm means right heart-failure, and since this comes late in the course of hypertensive failure it is a significant finding. It was found to be a useful clinical guide to the presence of rightsided enlargement in thyrotoxicosis and congenital heart disease as well as in emphysema, in which it carried a grim prognosis, 4 out of 5 patients dying within five months of its detection. Type 2 is similarly subdivided into two subgroups, a being often of little significance and b a serious omen. Of the 60 patients with type 2 showed 14 rhythm type 2a, where the extra sound is auricular systole when there is delay in produced by auriculo-ventricular conduction. In these cases the triple rhythm is best heard slightly inside the mitral area with the patient down, but it can also be heard in the erect position. After full examination 6 of the 14 patients were passed as healthy. Not all
lying
patients with sufficient auriculo-ventricular delay to prolong the P-R interval beyond the normal 0’2 sec. will show triple rhythm, but nearly all young people will do so. Type 2b is the classical bruit de galop of older writers, and is always associated with left ventricular failure. Of EvANS’s 46 patients with this type of triple rhythm, 41 had hypertension and 5 aortic incompetence, the low proportion of cases of aortic incompetence agreeing with GARVIN’s experience.4 Here the sound is probably produced by the shock of the auricular blood wave on a hypotonic This type of rhythm therefore means ventricle. left ventricular failure with a normally contracting The added sound is heard best along a auricle. line running from the displaced apex beat to the left border of the xiphisternum, and is often accentuated by a rapid heart-rate ; it is loudest with the patient lying down, but can be heard in the erect position. It can most easily be detected by placing the ear direct on the chest, when the sound is well heard and the characteristic dual impulse can be felt. In type 3 triple rhythm a dull and muffled or sometimes clicking sound is heard immediately before the second heart sound. EvANS found it in only 5 of his patients, and in none of them was there any evidence of heart disease. This small but important field of clinical medicine had become the battlefield of the experts, whose disputations gave the clinician little help in assessing the significance of the extra sounds he hears occasionally in the heart. EVANS’S study will encourage us to detect and help us to explain the triple rhythms, and it should reduce the number of people who, apparently the picture of health, are told as youngsters that there is " something wrong with their heart." 4.
Garvin, C. F. Amer. J. med. Sci. 1943, 205, 814 (see Lancet, 1943, ii, 199).
PHARMACEUTICAL POCKET Booxi We cannot pretend to the value of this book (Pharmaceutical Press. 10s.) to the pharmacist except to remark that it is now in its 14th edition. - We are entitled to regard it as a guide to the kind of help the practitioner may expect to get from his friend in the chemist’s shop, and there are many things in the attractive little volume of 400 pages which the practitioner who has not got them at his fingers’ ends will be heartily glad to know that someone has. Few doctors, for example, know their poisons rules, let alone the laws relating to patents and trademarks, and the prescriber must leave it to the pharmacist to ensure that the liquor arsenicalis he orders really does contain gr. 87t to the pint. assess
.
VACCINATION AGAINST MEASLES
diverse routes-by intranasal instillation, 1 c.cm. into each nostril ; by inhalation, 1 c.cm. atomised DESPITE early success against smallpox and rabies directly beneath the nose into a cellophane" shower active immunisation against virus infections has in cap " covering the child’s head, making a barely general been slow and beset with difficulties. Even visible fog containing no large droplets ; by the against influenza and poliomyelitis, on both of subcutaneous route alone or combined with the nasal which much study has been concentrated, the progress route ; and by intradermal injection, 0’2-1 c.cm. of achieved has disappointed early hopes. In the light 1 in 10 to 1 in 10,000 dilutions according to the of these experiences the recent attempts to confer number of egg passages. Finally, upwards of 27 immunity against measles by means of attenuated groups of children comprising the vaccination experi. virus vaccination must be studied critically. Nor ments were subdivided into two groups of presumed should the previous work on measles itself be forthose had been under constant who susceptibles ; (a) gotten. In 1759 HOME1 claimed to have protected medical supervision from birth, and (b) those not susceptibles against attack by scarifying them with so well looked after, in whom an attack of measles assumedly infective blood taken from patients who have been overlooked or forgotten. Measles had recently had measles, but subsequent workers might of varying severity followed inoculation in 74% of could not confirm this observation. HERMANN2 in the 255 children inoculated, and if 32 doubtful cases 1914 instilled filtered nasopharyngeal washings into are included the figure rose to 92%. The incubation the anterior nares of babies 3-5 months old in order was period usually shorter (6-7 days) than in natural to raise and perpetuate the passive immunity they but occasionally it was prolonged. The measles, are assumed to derive from their mothers, but the observers were impressed by the paucity and mildmethod was soon abandoned because unmodified ness of symptoms, especially the almost complete attacks were too frequent and dangerous to be absence of cough, although the rash was sometimes disregarded. HIRARSHI and OKAMOTA3 in 1921, brilliant and the temperature high but transient. and later DEBBE and his associates,4 claimed to have As regards efficacy of route, intranasal drip returned induced by the inoculation of various dilutions of only 30% positive " takes," compared with 80% blood from measles patients attenuated attacks after intradermal injection and 98% with the inhaled conferring an immunity sufficient to render the spray. Of 35 presumed non-immunes who were inoculated insusceptible to further injections. Apart regarded as unsuitable for vaccination but were from their inherent risk these experiments were exposed to subjects with an attenuated attack, necessarily limited in scope and application since 16 showed no response, 6 were doubtful and 13 had fresh blood had to be used for each inoculation. For attacks similar to those in the inoculated-in other 20 years the limited success which has attended the words, there was no reversion to unattenuated or use of immune measles serum (convalescent, placental normal measles, at least by one human passage. and normal adult) in the prevention and modification A reporton 22 children observed for a year after of measles has diverted the attention of workers in successful vaccination shows that, after chance this field from active prophylactic methods, but in exposure, 15 did not contract measles, 3 had unmodithe last 5 years the researches of PLOTZin France fied attacks, 1 had an extremely mild attack and in and of STOKES and RAKE 6 in America on the 3 the disease was so mild as to be identified with cultivation of measles virus on the chorioallantoic difficulty. An illustration of the protection afforded membrane of the developing chick embryo, and their was given by a group of 7 vaccinated children who demonstration of attenuation of the virus by repeated escaped entirely, in contrast to 25 attacks among egg-passages, first on monkeys and later on sus- 36 unvaccinated but otherwise similar children ceptible humans, has raised hopes that a practicable exposed in the same school. An additional 24 method of active immunisation has at last been children of the vaccinated group were given challenge discovered. of blood taken from active cases of measles ; injections The new antigen has been tried in Philadelphia in in 13 no disease followed, in 3 there was typical collaboration with field workers.’ Although egg- measles, in 2 mild attacks and in 5 mild extremely passage attenuated virus had previously been attacks ; 6 unvaccinated children given similar assayed on monkeys (Maccacus mulatta is a convenient challenge injections all developed typical unmodified animal and uniformly susceptible) the conditions of measles. RAKE 9 reports on two further trials the experiments now recorded were altered so fre- conducted since July, 1943, for the board investiquently that often there were insufficient numbers gating epidemic diseases in the Army. In Baltimore in a particular group of trials for the validity of the 827 coloured children assumed to be susceptible findings to be assessed. Virus of from 3 to 66 serial from the parents’ history were vaccinated ; of 412 passages was used in different experiments, the 26th of these who were carefully followed up, 145, or to 40th passage-virus being most constant in effect. 35%,’showed definite signs of mild measles. The The material was either kept frozen at -35° C. and number may have been greater, for a faint rash is thawed immediately before inoculation, or was readily overlooked in negroes. In Philadelphia 199 desiccated from the frozen state and reconstituted white children who had never had measles according to its original volume ; this procedure did not demonto their physicians’ records were vaccinated, and 172 strably alter activity. Inoculations were given by followed up ; of these, 131, or 76%, gave an equally 1. Home, F. Medical Facts and Experiments, London, 1759, p. 253. satisfactory response, the higher percentage being 2. Hermann, C. Arch. Pediat. 1914, 31, 885. ascribed to the more accurate history. 3. Hirarshi, S. and Okamota, K. Jap. med. World, 1921, 1, 10. 4. Debré, R. and Ravina, A. Bull. Soc. méd. Hôp. Paris, 1923, Summing the vaccinations to date, 1281 children 46, 226. have been inoculated without untoward effect; 5. Plotz, H. Bull. Acad. Méd. Paris, 1938, 119, 598.
VACCINATION AGAINST MEASLES
’
6. Stokes, J. and Rake, G. Science, 1940, 92, suppl. p. 10. 7. Stokes J., O’Neil, G. C., Shaffer, M. F., Rake, G. and Maris, E. P. J. Pediat. 1943, 22, 1.
Rake, G., Stokes, J., Shaffer, M. F. and O’Neil, 9. Rake, G. Ibid, 1943, 23, 376. Ibid, p. 17.
8. Maris, P.,
G. C.
729
TRIPLE RHYTHM
839 of them were carefully investigated revealing that 450 (54%) had definite evidence of modified measles. The absence of a clinical or serological test of immunity is a serious but not crucial handicap in assessing the efficacy of the measure. The sample of 40 proved protected out of 46 at intimate risk is impressive but not conclusive, since natural immunity remains a possibility ; an extended trial under ex. acting conditions should certainly be made, especially as the method has the virtue of being innocuous.
TRIPLE RHYTHM WORK done at oir JAMES MACKENZIEold departHospital goes far to explain the
ment at the London
significance of triple heart rhythm-‘the cadence produced when three sounds recur in successive cardiac cycles," as Evgrrs defines it in his Strickland Goodall lectured He has studied by phonocardiography the heart sounds in 270 patients over the age
,
of 9 years who were either known to have heart disease or were sent to his department for an opinion on their heart, and were found on auscultation to have triple rhythm.. No phonocardiogram was taken unless triple rhythm was first detected by the stethoscope, and his survey does not deal with splitting of the first sound at the apex or of the second at the base of the heart. He now suggests that terms like " gallop rhythm " should be discarded, and that we should speak of three types of triple rhythm. In type 1 the added sound is found early in diastole, immediately after the second sound (lub dupty-); it is the third sound of the normal cardiac cycle. In type 2 the extra sound comes late in diastole (tylub dup-) and corresponds to the fourth sound of the cardiac cycle. In type 3 it comes towards the end of systole, just before the second heart sound (lub tydup-). Types 1 and 2 are each divided into two subgroups. There were 205 patients with triple rhythm type 1, of whom 125 seemed healthy (la) and 80 had evidence of some form of heart disease (lb). The healthy ones were mostly young people, none being over 40, and it may be recalled that MANNHEIMFR2 found a third heart sound by phonocardiography in 70% of healthy These patients’ extra sound was best children. heard midway between the nipple line and the lateral border of the sternum, and was accentuated when the pulse was quickened or the patient lay down. In agreement with BRAMWELL’s observationcardioscopy showed a prominent pulmonary artery in most of these patients-47 out of 50 consecutive patients showed such a prominence, compared with 7 out of 50 controls of the same age-group with dual rhythm. In type 1b the extra sound was best heard in the mitral area or external to it, and it could usually be heard with the patient sitting up as well as lying down. It occurred in older patients than type la and was associated with lesions that produce enlargement and failure of the right side of the heart, such as
mitral stenosis, hypertension, thyrotoxicosis,
congenital heart disease, emphysema and pulmonary hypertension. In mitral stenosis the triple rhythm was commoner
with auricular fibrillation than with
rhythm, and its presence pointed to considerable enlargement of the right side of the heart. In hypersinus
1. Evans, W. Brit. Heart J. 1943, 5, 205. 2. Mannheimer, E. Acta pœdiatr., Stockh. 1940,
Lancet, 1941, i, 607).
28, suppl. 2 (see
3. Bramwell, C. Brit. Heart J. 1943, 5, 24 (see Lancet, 1943, ii,
279).
tension this type of rhythm means right heart-failure, and since this comes late in the course of hypertensive failure it is a significant finding. It was found to be a useful clinical guide to the presence of rightsided enlargement in thyrotoxicosis and congenital heart disease as well as in emphysema, in which it carried a grim prognosis, 4 out of 5 patients dying within five months of its detection. Type 2 is similarly subdivided into two subgroups, a being often of little significance and b a serious omen. Of the 60 patients with type 2 showed 14 rhythm type 2a, where the extra sound is auricular systole when there is delay in produced by auriculo-ventricular conduction. In these cases the triple rhythm is best heard slightly inside the mitral area with the patient down, but it can also be heard in the erect position. After full examination 6 of the 14 patients were passed as healthy. Not all
lying
patients with sufficient auriculo-ventricular delay to prolong the P-R interval beyond the normal 0’2 sec. will show triple rhythm, but nearly all young people will do so. Type 2b is the classical bruit de galop of older writers, and is always associated with left ventricular failure. Of EvANS’s 46 patients with this type of triple rhythm, 41 had hypertension and 5 aortic incompetence, the low proportion of cases of aortic incompetence agreeing with GARVIN’s experience.4 Here the sound is probably produced by the shock of the auricular blood wave on a hypotonic This type of rhythm therefore means ventricle. left ventricular failure with a normally contracting The added sound is heard best along a auricle. line running from the displaced apex beat to the left border of the xiphisternum, and is often accentuated by a rapid heart-rate ; it is loudest with the patient lying down, but can be heard in the erect position. It can most easily be detected by placing the ear direct on the chest, when the sound is well heard and the characteristic dual impulse can be felt. In type 3 triple rhythm a dull and muffled or sometimes clicking sound is heard immediately before the second heart sound. EvANS found it in only 5 of his patients, and in none of them was there any evidence of heart disease. This small but important field of clinical medicine had become the battlefield of the experts, whose disputations gave the clinician little help in assessing the significance of the extra sounds he hears occasionally in the heart. EVANS’S study will encourage us to detect and help us to explain the triple rhythms, and it should reduce the number of people who, apparently the picture of health, are told as youngsters that there is " something wrong with their heart." 4.
Garvin, C. F. Amer. J. med. Sci. 1943, 205, 814 (see Lancet, 1943, ii, 199).
PHARMACEUTICAL POCKET Booxi We cannot pretend to the value of this book (Pharmaceutical Press. 10s.) to the pharmacist except to remark that it is now in its 14th edition. - We are entitled to regard it as a guide to the kind of help the practitioner may expect to get from his friend in the chemist’s shop, and there are many things in the attractive little volume of 400 pages which the practitioner who has not got them at his fingers’ ends will be heartily glad to know that someone has. Few doctors, for example, know their poisons rules, let alone the laws relating to patents and trademarks, and the prescriber must leave it to the pharmacist to ensure that the liquor arsenicalis he orders really does contain gr. 87t to the pint. assess
.