614

PORTS OF ENTRY IN POLIOMYELITISTHE opening of the poliomyelitis season is a, reminder

that recent experimental work, particularly in theUnited States, has helped to narrow down the problemsrelating to the transit of the virus to the central nervoussystem. Fairbrother and Hurst, in 1929, demonstratedthat the virus of poliomyelitis spreads along the axis-cylinders, involving different tracts in the brain serially,and their important work has since been expanded andmodified. In their monkeys the nervous system wasinfected by way of the olfactory tract after intranasalinoculation ; from this the idea has taken root in manyquarters that infection in man adopts the same path.Bodian and Howe,! among others, have confirmed that theaxis-cylinders are the lines of communication of thevirus, but they have made it clear that ports of entryother than the nasal mucosa should be considered.Some of their evidence has been derived from the studyof arrested and non-paralytic examples in experimentallyinfected animals. Cases of these sorts unquestionablyoccur in man but their pathological anatomy naturallyevades investigation. Bodian and Howe describechanges in 2 chimpanzees and 3 rhesus monkeys which,after administration of the virus, showed spontaneousarrest of the infection with a corresponding limitation ofinflammation to foci within the central nervous system.Their first chimpanzee, after being inoculated in themouth with a virus suspension, developed, a month later,a febrile reaction lasting 24 hours. This was accom-panied by a pleocytosis in the lumbar spinal fluid andwas followed a day later by a mild and transient leftfacial paralysis. When the chimpanzee was killed fourdays after this, the inflammatory reaction was found tobe limited to the gasserian ganglia and to foci in themedulla oblongata and cervical cord including thetrigeminal centres and left facial nucleus. Thus thedisease had apparently been arrested before the charac-teristic distribution of the inflammatory changes wascomplete. The second chimpanzee received an intra-nasal inoculation of the virus and died about a weeklater of pulmonary tuberculosis, without displaying anyclinical signs of poliomyelitis ; but microscopic changescharacteristic of poliomyelitis were present in the brain,restricted to the olfactory bulbs and secondary olfactorycentres.The site of the lesions within the nervous system in

these 2 chimpanzees thus bore a significant relation to thesite of the inoculation and this was again shown in the 3rhesus monkeys which were inoculated intranasally and,after a febrile response, developed no paralyses. Histo-logical examination at periods from one to three weekslater showed restriction of the lesions to the olfactorybulbs, secondary olfactory centres and hypothalamus.In, all probability similar localised but arrested inflam-mations occur in man. Howe and Bodian have investi-gated the relations between the sites of inoculation andassociated changes in the central nervous system in afurther group of 6 chimpanzees. 2 In this group, 2 wereinoculated by the olfactory, 2 by the oral and 2 by thegastro-intestinal route. One member Qf each of the lasttwo pairs had the olfactory tracts divided by a prelimin-ary intracranial operation. The resulting attacks ofpoliomyelitis were milder than those produced by asimilar dosage in rhesus monkeys and resembled clinicalexamples commonly seen in man. All the animals werekilled in the acute stage of the disease. Histologicalexamination showed a distribution and intensity ofencephalomyelitis which were evidently related to theport of entry of the virus : thus lesions in the olfactorytract were present only in the animals receiving intra-nasal inoculations while those inoculated in the mouthshowed a heavy involvement of the bulbar region, thefifth and possibly the ninth nerves being especiallyimplicated in one animal. In the animals infected byway of the stomach there was histological evidence thatthe virus had reached the spinal cord first and the brainlater. A further point of interest in these experimentswas that the virus could be demonstrated in the stoolswith nearly as much regularity as it can in man. In thisthe chimpanzee differs from the rhesus monkey which is

1. Bodian, D. and Howe, H. A. Bull. Johns Hopk. Hosp. 1941 69,135.

2. Ibid, p. 149.

not susceptible to infection by gastro-intestinal inocula-tion,-and this helps to support the opinion that, where thecourse of the disease is concerned, zoological affinitycarries some weight.

APPLICATION TO MAN

Howe and Bodian have analysed the lesions in 13 humanbrains obtained from rapidly fatal cases or cases dying inlate stages of the acute illness.3 They found, like earlierobservers, that lesions in the olfactory bulbs and second-ary olfactory centres were rare, and that the evidence,taken as a whole, pointed to ingress of the virus by themouth, pharynx or intestinal tract. The relatively latestage of the disease in these cases unfortunately made itimpossible to establish the port of entry more narrowlythan this ; but in cases showing an initial bulbar paraly-sis it may be supposed that the oro-pharyngeal mucosawas the site. Sabin 4 mentions, in a recent symposiunion poliomyelitis, that during the last ten years a relativelylarge number of cases of bulbar poliomyelitis have beenreported as occurring shortly after tonsillectomy or

adenoidectomy performed when poliomyelitis was

prevalent. The evidence for the gastro-intestinal tractas a portal lacks precision but it does seem likely, fromthe anatomical findings in man, that the virus travelsfrom the gut to the spinal cord by way of the sympatheticnerves and by way of the vagus nerve to the medulla’oblongata. Sabin and Ward, in mapping out the distri-bution of poliomyelitis virus in human tissues, have foundthat it is mainly confined to the nervous system and thealimentary tract, but is not distributed indiscriminatelyin either ; in<the nervous system it is found in areas thathave undergone pathological alteration, while in thealimentary tract it predominates in the pharynx andileum. In the absence of any evidence of centrifugalspread of the virus from the central nervous system toperipheral parts, Sabin considers that the intestinaltract is the probable port of entry and that in general theolfactory, respiratory and cutaneous routes can be disre-garded. A case of poliomyelitis in a laboratory workerwho had been handling the virus, reported elsewhere bySabin and Ward is of interest in this connexion. Thevictim had been washing and grinding tissues frominfected cynomolgus monkeys, and the attack-whichwas accompanied by paralysis first of the right leg andlater of other limbs-was fully proved to be poliomyelitis.Much has still to be learnt of the methods by which

virus can travel in the sympathetic system and peripheralnerves. That it does travel in the sympathetic chainsappears from the finding by several workers, and con-firmed by Howe and Bodian,6 that transection of thespinal cord will not prevent the progress of virus beyondthe level of division. But the virus still spreads in animalssympathectomised at the level of transection, apparentlyvia sympathetic fibres to the gut and thence by the vagusnerve to the brain stem. The same workers estimate’the rate of travel of virus along the axon to be 2-4 mm. perhour, a figure which may be compared with the rate of4-5 cm. in four hours ascribed to methylene-blue byPerdrau in 1937.

SUPPLEMENT ON ECONOMY IN DRUGSTHE therapeutic requirements committee of the

Medical Research Council have added a supplement toWar Memo. No. 3 (Economy in the Use of Drugs inWar-time), in which additions are made to the classified’lists and the categories of certain drugs (indicated by anasterisk in the following list) are changed. The additionsare mostly drugs to which approved names have beenallotted since the publication of the memo, but someherbal remedies have been added to category C. Thesubstitutes or equivalents suggested are given inparentheses.

(A) Drugs which are either regarded as essential or readilyavailable.-Amethocaine, diphenan, coconut oil, hexazole,menaphthone (synthetic vitamin K, 2-methyl-l : 4-naphthoquinone), mesulphen, orthocaine, soluble phenytoin(sodium diphenylhydantoinate), pholedrine, Pirevan, Piroparv,pyrethrum, safrole, and a large number of sera and vaccines.

3. Ibid, p. 183.4. Sabin, A. B. J. Amer. med. Ass. 1941, 117, 267.5. Sabin and Ward, R. Science, 1941, 94, 113.6. Bull. Johns Hopk. Hosp. 1941, 69, 86.7. Ibid, p. 79.