150
lateral sclerosis in the Mariana Islands of the SouthPacific 11
and in the discovery of a new disease of thenervous system, kuru,12
affecting natives in the easternhighlands of New Guinea.A third
example of the importance of neurological
research in the tropics is the description, during the
pastdecade, by CRUICKSHANK and his colleagues in theUniversity of
the West Indies, of " Jamaican para-plegia ".13-1 The investigation
of this puzzling chronicdisorder in Jamaican adults illustrates the
many diffi-culties in the way of clinical research in local
com-munities. The syndrome has five main elements arisingin
different combinations: damage to the pyramidaltracts and posterior
columns of the spinal cord; selectivelower-motor-neurone lesions,
retrobulbar neuropathy,and nerve deafness. The condition is also
found in otherCaribbean islands and has some features in commonwith
the myelopathies discovered in Africa and the FarEast. The latest
report 18 from Jamaica is based on ananalysis of 206 cases and 11
necropsies. There seem tobe two distinct groups: ataxic (25 cases)
and spastic(181 cases). The cases that came to necropsy belongedto
the spastic group. In the ataxic group there was ahigh incidence of
optic atrophy and eighth-nervedeafness, with slight evidence of
pyramidal-tractdamage. Patients in this group were poorly
nourished.In the larger spastic group the incidence of optic
atrophyand eighth-nerve deafness was relatively low.
Thehistopathological findings in the spastic cases werethose of a
chronic meningomyelitis, with damage to thelong tracts as the major
lesion.
In Africa and the Far East these and similar syndromeshave
usually been confined to malnourished people, butin Jamaica, in the
spastic group, nutrition seemed to besatisfactory. Toxic elements
in the diet have beenconsidered, in view of the resemblance to
lathyrism andthe widespread consumption in the Caribbean of "
bushteas ", some of which have been incriminated in anotherJamaican
syndrome-veno-occlusive disease of theliver. But no connection has
been traced between anyof the native plants and these neurological
disorders.The possibility that a treponema is responsible has
alsobeen closely examined. Random serum samples fromadult Jamaicans
have shown positive treponemal reactionsin 20-40%. In the ataxic
group the treponemal reactionsin the blood were negative in 64%; in
the cerebrospinalfluid they were negative in all cases, and there
was noabnormality of protein or cell content. On the otherhand, 60%
of the spastic group gave positive reactionsin the blood, although
in the cerebrospinal fluid they werepositive in only 6%. A moderate
increase in lympho-cytes and/or protein was found in 40% of cases.
TheArgyll-Robertson pupil was rare, and penicillin therapyfailed to
help the patient or to influence the cerebro-11. Kurland, L. T.
Proc. Mayo Clin. 1957. 32, 449.12. Gajdusek, D. C., Zigas, V. New
Engl. J. Med. 1957, 257, 974.13. Cruickshank, E. K. W. Ind. med. J.
1956, 5, 147.14. Cruickshank, E. K. Fed. Proc. 1961, 20, suppl. 7,
p. 345.15. Cruickshank, E. K., Montgomery, R. D. W. Ind. med. J.
1961, 10, 211.16. Cruickshank, E. K., Montgomery, R. D., Spillane,
J. D. World Neurol.
1961, 2, 199.17. Robertson, W. B., Cruickshank, E. K.,
McMenemey, W. H., Mont-
gomery, R. D. Proc. IV Int. Congr. Neuropath. 1962; vol. III, p.
434.18. Montgomery, R. D., Cruickshank, E. K., Robertson, W.
B.,
McMenemey, W. H. Brain, 1964, 87, 425.
spinal-fluid changes. Lastly, endarteritis obliterans,
thecharacteristic feature of neurosyphilis, was not
observed.Worldwide comparative studies will obviously be
necessary before the cause or causes of these obscuretropical
myelopathies and neuropathies are unravelled.They provide a fine
field of clinical research which shouldstir the imagination of
young neurologists in the develop-ing nations, and they offer
opportunities for inter-national liaison. The World Federation of
Neurologyhas already established a Commission on TropicalNeurology,
and the first international symposium washeld in Buenos Aires in
1961.19
Lathyrism has been known since the time of Hippo-CRATES. He
wrote:" at Ainos those men and women whocontinually fed on pulse
were attacked by a weakness inthe legs which remained permanent".
There is littledoubt that he would have been equally intrigued
byJamaican paraplegia.
Annotations
HEALTH OF IMMIGRANTS
OF the 300,000 people living in Bradford in 1963, about12,000
were immigrants from Asia. Of the 353 new casesof tuberculosis
reported during the year, 203 were inAsians 2; in other words, 4%
of the population accountedfor nearly 60% of the cases. Edgar 21
has shown thatnearly all these immigrants came from Pakistan.
InBirmingham, Springett 22 found that tuberculosis wastwenty-seven
times as common among Pakistani immi-grants as among the indigenous
population.
Stevenson 23 estimated that 50% of the immigrants
withtuberculosis in Bradford had contracted it since theirarrival
in this country; and Aspin 24 put the figure as highas 80% for
Indians in Wolverhampton. Their resistancemay be innately low: they
are subject to the stresses of analien environment; they live in
closed communities; evenwhen proper housing is available, our
inhospitable climatecrowds them together in search of warmth and
companion-ship. There is no evidence that the disease is spreading
tothe rest of the community, but this may be due only to thevery
isolation which is the greatest source of danger to theimmigrants
themselves.Our chest clinics may be able to deal with the
existing
and discovered cases, but unaided they cannot cope with asteady
influx of undetected new infection. All the authorswe have quoted
said that control was impossible unless allimmigrants had a chest
X-ray on or before arrival here-an opinion that we 25 and others 26
have supported.Moreover, the British Medical Association has
repeatedlyasked for compulsory X-ray examination on arrival 27
28;and Aspin 24 suggested that the examination should berepeated
annually.The Ministry of Health has now announced the
following arrangements to deal with the problem.19. Proceeding
of the First International Symposium of the Commission in
Tropical Neurology, World Federation of Neurology, Buenos
Aires,1961. Buenos Aires, 1963.
20. Douglas, J. Annual report of the medical officer of health,
Bradford,1963.
21. Edgar, W. Brit. med. J. 1964, ii, 1565.22. Springett, V. H.
Lancet, 1964, i, 1091.23. Stevenson, D. K. Brit. med. J. 1962, i,
1382.24. Aspin, J. ibid. p. 1386.25. Lancet, 1962, i, 843.26.
Tubercle, 1964, 45, 279.27. Brit. med. J. 1961, ii, 1624.28. ibid.
1964, ii, suppl. p. 211.
151
The chief medical officer has written to all general
practi-tioners in the Health Service asking them to look out
forimmigrants among their patients and to consider the need
toarrange for X-ray examinations.
Immigrants who are medically examined at ports and airportswill
be given a notice printed in languages they understand,encouraging
them to get on the list of a family doctor withoutdelay in the
district where they go to live, instead of waitinguntil they may be
ill. Medical inspectors at ports and airportswill seek from these
immigrants their destination addresses.These will then be sent to
the medical officers of healthconcerned asking them to arrange for
the immigrants to bevisited, told about the Health Service, and
advised to registerwith a family doctor. As far as possible the
addresses of thosenot subject to medical examination on arrival-for
example, thewives and children of some Commonwealth
immigrants-willalso be sent from the ports and airports to local
medical officersof health to give them the same information and
advice.At London Airport, where more long-stay immigrants
arrive
than anywhere else, X-ray apparatus is to be installed. Whenthe
medical inspectors suspect, for example, tuberculosis, theywill be
able to have an X-ray taken on the spot. If this confirmstheir
suspicion, they can then send information to the localmedical
officer of health. (If the X-ray reveals a dangerous caseof open
tuberculosis and the immigrant has not yet beenadmitted, the
medical inspector may recommend to theimmigration officer to refuse
entry.)Three years ago, referring to tuberculosis among
Pakistanis in Bradford, Stevenson 23 wrote: " We ... haveused
every possible method to get them to the X-raymachine-by
advertising at Pakistani film shows, and byhousehold canvassing,
lectures, and repeated street surveyswith the mobile X-ray van in
the Pakistani districts, allwithout much success." We wonder,
therefore, whethercards, telling people to get themselves on a
doctors list,will really be sufficient.The Governments view is that
medical inspection of
intending immigrants before they leave home is impractic-able.29
Is it also impracticable to do it when they arrive ?It has been
said that to examine Commonwealth immi-grants " would result in an
invidious distinction beingdrawn between them and aliens who are
not subjected toany such requirements ". But why should alien
immigrantsnot be examined? Could not areas. where tuberculosis
ishighly prevalent be so designated, as is already done
withsmallpox? And why should medical examination beregarded as
something obnoxious, instead of a service to ournew guests, done in
their own interests ? For it is they,and their compatriots here,
who are suffering.The new X-ray apparatus at London Airport will
not be
used as a matter of routine, but only to examine
suspiciouscases. This " should enable a clearer picture to be
obtainedof the extent to which immigrants may actually be
cominginto the country with tuberculosis ". But if it is to beused
only when a medical inspectors suspicions arearoused, it is
unlikely to prove more than that people wholook consumptive often
are.London Airport receives 21/2 million people every year,
and it may well be impossible to identify those who intendto
stay here and examine them on the spot; and there aremany other
ports of entry to be considered. Perhapsimmigrants could be
required to report to the nearestchest clinic when they reach their
new home, and notsimply advised to look for a family doctor.
Naturally, theGovernment is anxious to do nothing that appears
todiscriminate against these new arrivals. Rightly, the aim isto
treat them like anyone else, and the ultimate object mustbe to see
them assimilated by the community to which
29. See Lancet, 1964, ii, 1300.
they are making a valuable contribution. But beforeaccepting
them, the communities in which they live willwant to be further
assured that their own health is notbeing endangered.
ANTIVIRAL AGENTS
PESSIMISM has for long prevailed about the prospects offinding
effective antiviral agents, just as it did in thetwenties and early
thirties about the possibility of findingeffective in-vivo
antibacterial substances. But pessimism isgiving way to cautious
optimism, since at least two effectiveantiviral drugs are now
available commercially. The workwhich led to the discovery of
antiviral substances hasbeen reviewed from the clinical standpoint
by Stuart-Harris and Dickinson. There is great interest in
thissubject, not only because of the prospects for the cure
orprevention of virus disease but also because of the lightthat
antiviral agents shed on the processes of viralsynthesis. And this
interest was evident in the largeattendance at a meeting of the New
York Academy ofSciences on Dec. 9-11.One of the strongest
influences in the change of opinion,
about chemoprophylaxis at least, has been the work ofDr. D. J.
Bauer and his colleagues on methisazone in theprevention of
smallpox in those exposed to infection. Itwas appropriate therefore
that a whole session at themeeting was devoted to the
thiosemicarbazones; andDr. Bauer was awarded the A. Cressy Morrison
prize of theNew York Academy of Sciences for his paper on
clinicalexperience with methisazone. He reported the extensionof
his work on contacts of smallpox treated prophylacticallywith
methisazone to over 2000 in the treated and controlgroups, with
essentially the same results as before.2 Thus,there were 114 cases
and 20 deaths in the controls and 6cases and 2 deaths in the
treated group. In a smallgroup who had no prior vaccination there
were 28 casesand 11 deaths amongst 100 controls and only 2
casesamongst 102 treated contacts. Methisazone has beenshown in
tissue culture (in experiments described at themeeting by G.
Appleyard) to prevent the synthesis ofpox-virus proteins which
appear late in the virus growthcycle. In sufficient dosage, the
drug completely preventsthe synthesis of infectious virus; thus, a
relatively shortperiod of treatment should suffice, and Bauer
suggestedthat a period of two growth cycles was enough. Such ashort
treatment period may well be important in view ofthe severe nausea
and vomiting produced by methisazone,3which will discourage its use
except under severe threat.Indeed, the thiosemicarbazones were
abandoned asantituberculosis. drugs mainly because of their
toxicity.Of the thiosemicarbazones, methisazone is not the most
active against pox viruses. It was selected for initial
studybecause it was easier to make and more was known of
itstoxicity. Another thiosemicarbazone (M. & B. 7714),
whichAppleyard found had a mode of action similar to methisa-zone
but was slightly less active against rabbit pox, wastried by J. A.
McFadzean in a controlled trial for the treat-ment of smallpox. He
found that there were 42 deaths in132 control cases and 24 in 131
patients treated withM. & B. 7714, a difference which was not
statistically sig-nificant ; but C. H. Kempe thought that a larger
seriesconfined to early cases might well prove the value of this1.
Stuart-Harris, C. H., Dickinson, L. The Background to
Chemotherapy
of Virus Diseases. Springfield, Ill., 1964.2. Bauer, D. J., St.
Vincent, L., Kempe, C. H., Downie, A. W. Lancet,
1963, ii, 494.3. Landsman, J. B., Grist, N. R. ibid. 1964, i,
330. Hutfield, D. C., Csonka,
G. W. ibid. p. 329.