451 representative bodies. But the ultimate success of a national health service will depend on the vigour with which the plans are executed. Once the ques- tion of suppression of redundant inefficient institu- tions arises, there is a danger that representative bodies will split into groups according to the interests they represent. For a national health service to become maximally efficient in a minimum of time, its governors should probably be an appointed national non-representative board. This argument, however, will not convert those who believe that in the long run democratic control at all levels gives greater efficiency than a more authoritarian machine. ’FLU VACCINES UP THE NOSE FOR some years F. M. BURNET has pointed out the theoretical advantages of immunising against in- fluenza by spraying an attenuated but still living virus up the nose. In general, where live virus vaccines can be safely given they are more effective than killed ones ; moreover, in an emergency it would not be difficult to produce in a hurry a lot of influenza vaccine of the necessary type. In Australia attempts have been made to test intranasal ’flu vaccines in the fields Influenza viruses of three different strains were attenuated by amniotic passage in chick embryos and were administered by a de Vilbiss atomiser, each subject receiving 0.25 c.cm. Antibodies to the three virus strains were estimated, before and after the vaccination, by the Hirst test (inhibition of the agglu- tination of fowl red cells). About half those inoculated showed a rise in antibody titre against one or other virus-on the whole rather a poorer result than sub- cutaneous vaccination with inactivated influenza virus has produced here and in America. But it is urged that a virus given up the nose may produce antibody rise only in those in whom it can gain a foothold, in other words only in those susceptible persons whom we want to immunise ; we do not care whether or not antibodies increase in the others, who are immune anyway. In support of this seductive argument it is recorded that when vaccinated people who had shown a good antibody rise to an influenza B vaccine were revaccinated 3 to 6 months later very few showed any further rise. No epidemic occurred among them to put their immunity to a real test. One argument against the use of live attenuated influenza vaccines is based on a fear that they might increase in virulence by passage from man to man. There was no evidence that this happened in the Australian trials, either in those conducted during an influenza season or in those after it; the trials involved " tens of thousands " of soldiers. Reactions produced by the intranasal vaccines were frequent but almost all slight, mostly amounting to slight headache, coryza or stuffiness for a day or two, not going on to the muoopurulent stage which so often follows a real cold. Among the soldiers no reactions were bad enough to interfere with training. It is suggested that these reactions were allergic, as they were com- moner in those with an initially high antibody level than in those with a lower titre. They were also more in evidence after <8, second than after a primary vaccination ; the possibility of sensitisation to the chick embryo fluids is not discussed. 1. Burnet, F. M. Med. J. Aust, 1943, i, 385. Bull, D. R. and Burnet, F. M. Ibid, p. 389. Mawson, J. and Swan, C. Ibid, p. 394. There are virus-inactivating properties in human nasal secretions, and less certainly in tears, and these may have a great influence on liability to respiratory infection and response to intranasal vaccination. FRANCIS and others have lately found that the neutralising activity of nasal secretions rises after subcutaneous injection of inactivated influenza vac- cines, and suggest that on this, rather than on a rise in circulating antibodies as such, depends any value possessed by such vaccination. BURNET now reports the surprising discovery that freshly isolated human influenza strains differ from laboratory-adapted ones in not being neutralised by human tears ; he does not say whether nasal secretions also show up this difference. Other sharp differences between fresh and laboratory-trained strains were observed ; we must therefore be more cautious than ever in applying conclusions from the laboratory to the field. The Australian work is likely to be applied to the control of a pandemic rather than to the prevention of minor outbreaks such as we have had in recent years. Annotations TROPICS NOT SO UNHEALTHY IF— A REPORT from the medical department of a com- mercial airline operating a service from Bathurst, West Africa, down the Coast to Lagos, thence inland through the Sudan to Egypt (a distance of almost 5000 miles) and finally to India, shows how knowledge can be used to prevent disease. The first 2000 miles took in the semi-jungle country of the West Coast of Africa where although the temperature rarely exceeded 90° F. the humidity was always high, the rainfall reaching in some parts 200 in. a year and the humidity in others not falling below.90% for several months on end. Crossing the African continent the temperature increased but humidity fell, until in the Sudan and Egypt real desert conditions were encountered with average maximum temperatures of 110-115° F. and wide diurnal variations of 60-80° F., while in the Persian Gulf temperatures reached as much as 127° F. Candidates for service with the airline were carefully selected and the age-limits were set at 18-45 years. A full clinical examination was supplemented by blood- counts, serological tests and X-ray, examination of the lungs. Some 16% of applicants were rejected, the chief causes being cardiovascular diseases (20%), visual defects (12%), genito-urinary diseases (11%), and respiratory conditions (10%) ; those having a history of repeated attacks of venereal disease, chronic alcoholism or peptic ulcer were also regarded as unsuitable types. Accepted applicants were inoculated against smallpox, the enteric fevers, tetanus, yellow fever and cholera, and were provided with mosquito nets, anti-mosquito clothing, a sun helmet, and a supply of quinine and mosquito- repellant before sailing. Of the men sent to Africa less than 3% returned for medical reasons and none of these was seriously incapacitated. In Africa, hospital-bed accommodation was provided for 10% of the personnel, but in fact 1% sufficed. In large stations a medical and surgical officer was provided for each 600 men, but a doctor was posted to each station even when the numbers there were small. Well-trained laboratory staffs and adequately equipped hospitals with properly planned departments, including laundry services,, played their part. 2. Francis, T. jun., Pearson, H. E., Sullivan, E. R. and Brown, P. M. Amer. J. Hyg. 1943, 37, 294. 3. War Medicine, 1943, 3, 484 and 619.
Transcript
451
representative bodies. But the ultimate success ofa national health service will depend on the vigourwith which the plans are executed. Once the ques-tion of suppression of redundant inefficient institu-tions arises, there is a danger that representativebodies will split into groups according to the intereststhey represent. For a national health service tobecome maximally efficient in a minimum of time,its governors should probably be an appointednational non-representative board. This argument,however, will not convert those who believe that inthe long run democratic control at all levels givesgreater efficiency than a more authoritarian machine.
’FLU VACCINES UP THE NOSE FOR some years F. M. BURNET has pointed out the
theoretical advantages of immunising against in-fluenza by spraying an attenuated but still living virusup the nose. In general, where live virus vaccinescan be safely given they are more effective thankilled ones ; moreover, in an emergency it wouldnot be difficult to produce in a hurry a lot of influenzavaccine of the necessary type. In Australia attemptshave been made to test intranasal ’flu vaccines in thefields Influenza viruses of three different strainswere attenuated by amniotic passage in chick embryosand were administered by a de Vilbiss atomiser, eachsubject receiving 0.25 c.cm. Antibodies to the threevirus strains were estimated, before and after thevaccination, by the Hirst test (inhibition of the agglu-tination of fowl red cells). About half those inoculatedshowed a rise in antibody titre against one or othervirus-on the whole rather a poorer result than sub-cutaneous vaccination with inactivated influenza virushas produced here and in America. But it is urgedthat a virus given up the nose may produce antibodyrise only in those in whom it can gain a foothold,in other words only in those susceptible persons whomwe want to immunise ; we do not care whether or notantibodies increase in the others, who are immuneanyway. In support of this seductive argument itis recorded that when vaccinated people who hadshown a good antibody rise to an influenza B vaccinewere revaccinated 3 to 6 months later very few showedany further rise. No epidemic occurred among themto put their immunity to a real test.One argument against the use of live attenuated
influenza vaccines is based on a fear that they mightincrease in virulence by passage from man to man.There was no evidence that this happened in theAustralian trials, either in those conducted during
,
an influenza season or in those after it; the trialsinvolved " tens of thousands " of soldiers. Reactionsproduced by the intranasal vaccines were frequent butalmost all slight, mostly amounting to slight headache,coryza or stuffiness for a day or two, not going on tothe muoopurulent stage which so often follows a realcold. Among the soldiers no reactions were badenough to interfere with training. It is suggestedthat these reactions were allergic, as they were com-moner in those with an initially high antibody levelthan in those with a lower titre. They were also morein evidence after <8, second than after a primaryvaccination ; the possibility of sensitisation to thechick embryo fluids is not discussed.1. Burnet, F. M. Med. J. Aust, 1943, i, 385. Bull, D. R. and
Burnet, F. M. Ibid, p. 389. Mawson, J. and Swan, C. Ibid,p. 394.
There are virus-inactivating properties in humannasal secretions, and less certainly in tears, and thesemay have a great influence on liability to respiratoryinfection and response to intranasal vaccination.FRANCIS and others have lately found that theneutralising activity of nasal secretions rises aftersubcutaneous injection of inactivated influenza vac-cines, and suggest that on this, rather than on a risein circulating antibodies as such, depends any valuepossessed by such vaccination. BURNET now reportsthe surprising discovery that freshly isolated humaninfluenza strains differ from laboratory-adapted onesin not being neutralised by human tears ; he doesnot say whether nasal secretions also show up thisdifference. Other sharp differences between freshand laboratory-trained strains were observed ; we
must therefore be more cautious than ever in applyingconclusions from the laboratory to the field.The Australian work is likely to be applied to the
control of a pandemic rather than to the preventionof minor outbreaks such as we have had in recentyears.
Annotations
TROPICS NOT SO UNHEALTHY IF—
A REPORT from the medical department of a com-mercial airline operating a service from Bathurst, WestAfrica, down the Coast to Lagos, thence inland throughthe Sudan to Egypt (a distance of almost 5000 miles)and finally to India, shows how knowledge can be usedto prevent disease. The first 2000 miles took in thesemi-jungle country of the West Coast of Africa wherealthough the temperature rarely exceeded 90° F. thehumidity was always high, the rainfall reaching in someparts 200 in. a year and the humidity in others notfalling below.90% for several months on end. Crossingthe African continent the temperature increased buthumidity fell, until in the Sudan and Egypt real desertconditions were encountered with average maximumtemperatures of 110-115° F. and wide diurnal variationsof 60-80° F., while in the Persian Gulf temperaturesreached as much as 127° F.
Candidates for service with the airline were carefullyselected and the age-limits were set at 18-45 years. Afull clinical examination was supplemented by blood-counts, serological tests and X-ray, examination of thelungs. Some 16% of applicants were rejected, the chiefcauses being cardiovascular diseases (20%), visual defects(12%), genito-urinary diseases (11%), and respiratoryconditions (10%) ; those having a history of repeatedattacks of venereal disease, chronic alcoholism or pepticulcer were also regarded as unsuitable types. Acceptedapplicants were inoculated against smallpox, the entericfevers, tetanus, yellow fever and cholera, and wereprovided with mosquito nets, anti-mosquito clothing, asun helmet, and a supply of quinine and mosquito-repellant before sailing. Of the men sent to Africa lessthan 3% returned for medical reasons and none of thesewas seriously incapacitated. In Africa, hospital-bedaccommodation was provided for 10% of the personnel,but in fact 1% sufficed. In large stations a medical andsurgical officer was provided for each 600 men, but adoctor was posted to each station even when the numbersthere were small. Well-trained laboratory staffs andadequately equipped hospitals with properly planneddepartments, including laundry services,, played theirpart.
2. Francis, T. jun., Pearson, H. E., Sullivan, E. R. and Brown, P. M.Amer. J. Hyg. 1943, 37, 294.
3. War Medicine, 1943, 3, 484 and 619.
452
In West Africa, where malaria is rife, military statisticssuggested that an attack-rate of 100% per annum, and’in some parts even 200%, might be anticipated. However,apart from an outbreak in the first few weeks of hurriedassembly-when 46 of 284 men were attacked, andalmost 2000 days of work were lost by 300 men in 11 1weeks-the malaria-rate proved extremely low. In
September, 1942, there was only one case among 1400employees and in October only 3 among 1800. Thiswas attributed to the aggressive antimalarial measuresapplied at all the stations of the line. Besides thepersonal protective measures taken by the staff, all
quarters and accommodation were screened and mainten-ance men were employed whose sole duties were to keepthe screening in order. Antimosquito locks of adequateproportions were provided for all entrances, which werekept to the minimum, and all doors were fitted withautomatic spring-closing devices. Quarters were sprayeddaily and the adjacent native quarters were similarlytreated. Oiling, dusting and drainage of potentialbreeding areas were also carried out and continuousmaintenance gangs looked after these works ; some 45miles of ditches were dug in one station alone. Flyingpersonnel had blood-examinations before every flightand the value of this was proven by the fact that innearly every instance where positive smears were
obtained the subject developed a clinical attack within24 to 48 hours. In the treatment of the acute attacksvarious combinations of drugs were tried without anystriking differences in the therapeutic results, and finallya routine course of quinine, gr. 30 daily for 2 days,followed by mepacrine hydrochloride, 0-3 g. daily for5 days, was adopted. Almost all the infections weremalignant tertian and it was not considered that any-thing was lost by the omission of pamaquin from thetreatment. Quinine and mepacrine were used in sup-pressive treatment and no evidence was forthcoming thatmepacrine diminished tolerance to altitude.
Gastro-intestinal diseases were next in frequency tomalaria, and were well controlled by the screening ofmesses, kitchens and latrines against flies. Before thiswas done some 20% of the personnel at one stationcontracted diarrhoea once or twice a month ; and inanother station the rate fell from 30% to 0 on theinstallation of flush toilets and the screening of quartersand kitchens. The importance of periodic examinationsof all native food handlers was shown by the fact that28% of the natives were found to be carriers ofE. histolytica.
Psychiatric problems, often stressed as a cause oftrouble in the tropics, were found to be relatively un-important ; *but all the personnel were volunteers andtheir living conditions and food were unusually good.Surgery presented no special difficulties and sepsis wasnot more common than in temperate regions. Themedical staff was convinced that the climate as such hadno deleterious effect on health and it was the unanimousopinion that good health can be maintained in thetropics provided preventive measures against diseaseare aggressively applied.
SENSITIVITY TO PAIN
PAIN is difficult to assess, and the word " sensitivity "is itself ambiguous, for both the man who feels littlepain and the one who feels the pain but bears it stoicallymay be called insensitive. Sherman refrains from adefinition, and waits for his patient to " wince, changeexpression, or cry out," in response to a gradually in-creasing painful stimulus. His instrument of torture(Hollander’s method) is a metal grater, with the businesssurface in contact with the subject’s arm, on which it ispressed by an inflated sphygmomanometer cuff. Thepressure at which the victim reacts spontaneously istaken as a measure of his threshold to pain, and he is-
1. Sherman, E. D. Canad. med. Ass. J. 1943, 48, 437.
accordingly classed as hypersensitive, hyposensitive ornormal. In spite of the errors likely to be involved inboth the stimulus and the reading of the response, anywell-marked difference between large groups of patientsexamined by the same investigator is probably significant.In two series, each of 130 patients, one group withorganic and one with functional disease, Sherman finds
practically the same proportion of hyposensitive persons(16-17%), while only 6%of patients with organic disease,as against 30% with functional, are hypersensitive. Theresults are confused by a sex difference, 75% of all thehypersensitive cases being women and 90% of the hypo.sensitive men, a finding possibly indicating only thatwomen are more thin-skinned than men. The fact that
34% of the hypersensitive cases are under 20 years ofage may be open to a similar interpretation. Corrobora-tion by Libman’s test of pressure on the styloid processcan scarcely be accepted, since there is no way of measur-ing the intensity of the stimulus. The differencebetween patients with functional and organic diseaseseems the most reliable finding, and is rounded off bythe study of a group of 150 exceptionally hardy men(coal-miners) who treated even organic disease withcontempt. None of them was hypersensitive, and 75%were hyposensitive. A similar distribution of sensiti.
vity in a group of Indians suggests that indifference topain may be inherited. An investigation of this kindis worth repeating with more precise methods. Routineclinical testing is one thing, but research to establish aprinciple is another. These results merely extend thoseof Wilder,2 who used the same method. An electricalstimulator described by Knowlton and Gross for study.ing analgesics in dogs would be little more troublesometo apply, but is quantitative, avoids the mixture ofsensations which must accompany the gradually increas-ing pressure of the grater in the sphygmomanometercuff, and allows of a rest between the increasing stimuli,thus eliminating the adaptation of the pain endingswhich must occur with a continuous stimulus. Re-
peated testing of the same individual on different daysshould also be done, because Knowlton and Gross founda certain variation of threshold in their dogs. They useda slight widening of the eyelids as indicative of the firstresponse to pain, and it is possible that in man some suchconsistent index could be found. From the .clinicalstandpoint, Sherman’s findings are useful confirmationof a general impression, but if they were further sub-stantiated they might lead to a reliable test for helpingto distinguish between functional and organic disorder.
TREATMENT OF METHÆMOGLOBINÆMIA
METH1EMOGLOBIN in the blood has been classicallyassociated with haemolytic diseases, certain, poisons, andenterogenous cyanosis. We now know that in hsemo-lytic diseases the pigment is methsemalbumin, but theother two are definitely methaemoglobinaemias, and thedistinction is easily made if one remembere that in
hsemolytic diseases the pigment is in the blood plasmawhereas in the others it is confined to the red blood-cell.There is one other very rare form of true methaemo-
globinsemia ; this is one of the " inborn errors of meta-bolism" and the victims have a varying proportion of theirblood haemoglobin in that form. They suffer no dis-ability, since the total blood-pigment is usually increasedso that the normal amount of oxyhaemoglobin is avail-able, but the presence of the methaemoglobin gives thema slaty-blue colour that is ugly, often exposes them tounnecessary investigation, and causes alarm. Thisdisease is so unusual that it might well remain buriedin the literature, but it now appears that, it can betreated. At a meeting of the Royal Academy of Medi-cine in Ireland on May 7, J. Deeny, H. Barcroft and D. C.Harrison described two brothers with this condition;2. Wilder, R. M., jun. Proc. Mayo Clin. 1940, 15, 551.3. Knowlton, G. C. and Gross, E. G. J. Pharmacol. 1943, 78, 93.
