The Etiology of Epidemic Poliomyelitis: Plates 6 – 8

A somewhat peculiar diplococcus or streptococcus has been found in the spinal fluid, and in the brain and cord of cases of poliomyelitis by various observers. In some instances injections in animals gave suggestive, although inconclusive results indicating the causal relationship of this organism. Other workers were unable to obtain corroborative evidence. Efforts to demonstrate bacteria in sections proved unsuccessful. The discovery that typical poliomyelitis can be produced in the monkey with so-called vims and filtrates of virus,^4,9,10 and the successful inoculation of monkeys by Flexner and Noguchi with the small “globoid” organism which they cultivated from the central nervous system in poliomyelitis, was considered final in proving that bacteria of ordinary size had no etiologic relation to this disease. The status of the question of the relation of these organisms, particularly streptococci, to poliomyelitis, when we began our studies is tersely stated by Wickman: “Such bacteria must be regarded as having had an accidental and not a causal relation to the malady.”

However, since the earlier studies were made, special methods have been developed and bacteria of ordinary size have been isolated from tissues which were considered sterile. The localization of these bacteria in animals frequently corresponded closely to that in the disease from which they were isolated. In view of these results, the older investigations were considered inconclusive as proving that bacteria of ordinary size had no etiologic relationship to poliomyelitis, and a restudy of the bacteriology of poliomyelitis by the use of the newer methods was undertaken.

We wish now to record the details of a study of a series of cases of poliomyelitis which occurred in Rochester, Minnesota, and New York City during the epidemic of 1916, and in Davenport, Iowa, in 1917. The results of the cases occurring in 1916 have been described in a preliminary report¹⁹ in which the following statement was made:

[missing text]…the tonsils was made in 38 cases. In 26 of these the cervical glands were enlarged, and in 11 the enlargement on either side was in proportion to the amount of infection in the tonsil on the corresponding side, as determined by the greater size of the tonsil or larger amount of infected material which could be expressed. In several instances these findings were verified at necropsy. No definite relation between infected conditions of the teeth could be made out although caries was present in some of the cases. The tonsils from 12 persons removed for various reasons in other diseases have been examined in the same way. The abscesses in the lymph follicles on cross section and the areas of necrosis noted microscopically in poliomyelitis were not found, although abscesses in crypts containing many organisms with atrophy of the epithelium were found in some of these.

The results of the study of the tonsils and adenoids here reported indicate strongly that these structures afford important entrance ways for the micro-organisms which we find constantly in the diseased tissues in poliomyelitis. A relatively large amount of infected material may be expressed from the tonsils. The abscesses and areas of necrosis are more numerous and are larger in the fatal cases than in tonsils removed from convalescent patients. These abscesses contain large numbers of this micro-organism, particularly in the fatal cases, and the cocci have been demonstrated in tissues immediately outside the tonsils, in areas of infiltration along large blood vessels and within the lumen of capillaries. Injection of cultures into animals produced flaccid paralysis. Removal of tonsils and adenoids in convalescent patients has been followed by seemingly good effects in some instances. In view of these facts there can be little doubt but that diseased tonsils and adenoids predispose to poliomyelitis and may lead in some instances to severe or fatal infection which might otherwise be mild. The focal areas of infection with abscess formation in these structures may be an important factor in prolonging an attack, in preventing early restoration of lost muscle function and be the cause of remissions or relapses which occur not infrequently as pointed out especially by Wickman and by Draper. The abscesses are usually small, and so situated mechanically as not to interfere with their healing. Protection by removal of these structures is only relative at best and temporary entrance channels for bacteria are made by their removal. Hence, their wholesale extirpation for protection against this dread disease would not be justified. Their removal in special instances may be useful, but the well established principles for the removal of tonsils and adenoids as applied in connection with other conditions should be followed in this disease.

Summary

A pleomorphic coccus has been isolated from and demonstrated in affected tissues in all the cases examined of poliomyelitis that occurred  in different epidemics and in widely separated parts of the country. The organism has been found in large numbers in adenoids and tonsils, in smaller numbers in lesions in various parts of the central nervous system, and in the mesenteric lymph glands. It has been proved to be absent in organs showing no lesions. The organism shows great variations in size and shape, depending on the method of cultivation. In aerobic cultures, although more irregular in size, it closely resembles ordinary green-producing streptococci or pneumococci of low virulence. Under anaerobic cultivation, especially in tall columns of ascites fluid plus tissue and oil, it grows to very small size, becomes filterable and every way appears identical with the “globoid” organism described by Flexner and Noguchi. The variations noted in cultures have been proved not to be due to contaminations or to mixed cultures. All gradations in size between large coccus or diplococcus forms to exceedingly small, almost ultramicroscopic forms, were found alike in cultures and in the tissues, and the conditions favorable for the formation of one from the other have been determined. Morphologic evidence of the breaking down of large forms into the small forms in the tissues has been obtained. Pure cultures of this organism have been isolated many times and it has been demonstrated in films and sections of brain and cord many months after they were placed in 50% glycerol. In view of these results the presence of this organism in the diseased tissues cannot be considered an accidental contamination.

The following facts, determined since the studies reported in this paper were begun, indicate that the organism here described bears etiologic relationship to poliomyelitis. It is constantly present in the diseased tissues, from which it can be cultivated even many months after glycerolation. On injections of cultures into young rabbits and guinea-pigs it localizes specifically in the nervous system and produces flaccid paralysis and changes in brain and cord which resemble those in poliomyelitis in man.²⁰ From the brain and cord of these animals the organism can be isolated and the disease again produced. The organism has been rendered filtrable. By means of the same methods the identical organism has been isolated constantly from the brain and cord of monkeys paralyzed with fresh, glycerinated and filtered virus.¹⁹ The serums of persons and of monkeys, having recovered from poliomyelitis, agglutinate specifically the more sensitive strains both from human and monkey poliomyelitis.¹⁸ Injections of the recently isolated aerobic cultures into monkeys renders them refractory to virus. The aerobic form of the organism from human and monkey poliomyelitis produces antibodies in the serum of horses, in a large amount common for both, cross-agglutinating these strains specifically in high dilution.¹⁰ The serum of a horse immunized with freshly isolated strains from monkeys protected monkeys relatively against intracerebral inoculation of virus¹⁶ and had pronounced curative effects in the treatment of human poliomyelitis. Early intravenous injections were followed by almost immediate cessation of symptoms in a large series of cases.¹⁷

The results of Flexner and Noguchi, so far as the cultivation of a small filtrable organism and its demonstration in the tissues in poliomyelitis are concerned, have been corroborated, but the results of our experiments indicate that this is the anaerobic and, according to most results, a non-antigenic form of the organism which, under aerobic cultivation, clearly belongs to the streptococcus group of microorganisms. Both forms have been constantly demonstrated side by side in the tissues of poliomyelitis. Flaccid paralysis coming on soon after injection has been produced in monkeys with characteristic, although not typical changes in the cord with aerobic cultures, but the classic picture as obtained with virus in this species has not been secured. It may be suggested, however, on the basis of results already obtained, that this is due to the development of antibodies, since the organism in the aerobic form has marked antigenic powers.

References Cited:

1. H. L.: “The cultivation and immunological reactions of the globoid bodies in poliomyelitis.” Jour. Exper. Med., 1917, 25, 545-555.
2. Blanton, W. B.: “An anatomical study of fifteen cases of acute poliomyelitis,” Med. Res., 1917, 36, 1-18.
3. Draper, G.: Acute poliomyelitis. Philadelphia, P. Blakiston’s Son and Co., 1917, 149 pp.
4. Flexner, S. and Lewis, P. A.: “The transmission of acute poliomyelitis to monkeys.” Am. Med. Assn., 1909, 53, 1639.
5. Flexner, S. and Noguchi. H.: “Experiments on the cultivation of the micro-organism causing epidemic poliomyelitis.” Exper. Med., 1913, 18, 461-485.
6. Hektoen, L., Mathers, G. and Jackson. L.: Microscopic demonstration of cocci in the central nervous system in epidemic poliomyelitis.” Infect. Dis., 1918, 20, 89-94.
7. Kolmer, J. A., Brown, C. P. and Freese, A. E.: “A contribution to the bacteriology of acute anterior poliomyelitis.” Exper. Med., 1917, 25, 789-806.
8. Kolmer, J. A. and Freese, A. E.: “Complement fixation in acute poliomyelitis.” Immunol., 1917, 2, 327-339.
9. Landsteiner, K and Levaditi, C.: “La transmission de la paralysie infantile aux singes.” rend. Soc. de biol., 1909, 67, 592-594.
10. Leiner, C. and Wiesner, R.: “Experimentelle Untersuchungen ueber Poliomyelitis acuta anterior.” klin. Wschnschr., 1909, 22, 1698-1701.
11. Mathers, G.: “Some bacteriologic observations on epidemic poliomyelitis.” Am. Med. Assn., 1916, 67, 1019.
12. Nuzum, J. W. and Herzog, M.: “Experimental studies in the etiology of acute epidemic poliomyelitis.” Am. Med. Assn., 1916, 67, 1205-1208.
13. Peabody, F. W., Draper, G. and Dochez, A. R.: “A clinical study of acute poliomyelitis.” Rockefeller Inst. Med. Res., 1912. No. 4, 1-187.
14. Robertson, H. E. and Chesley, A. J.: “Pathology and bacteriology of acute anterior poliomyelitis.” Int. Med., 1910, 6, 233-269.
15. Rosenow, E. C.: “The newer bacteriology of various infections as determined by special methods.” Am. Med. Assn., 1914, 63, 903-907.
16. Rosenow, E. C.: “The production of an antipoliomyelitis serum in horses.” Am. Med. Assn., 1917, 69, 261-265.
17. Rosenow, E. C.: “Report on the treatment of fifty-eight cases of epidemic poliomyelitis with immune horse serum.” Infect. Dis., 1918, 22, 319-426.
18. Rosenow, E. C. and Gray, H.: “Agglutination of the pleomorphic streptococcus isolated from epidemic poliomyelitis by immune horse, human, and monkey serum.” Infect. Dis., 1918, 22, 345-368.
19. Rosenow, E. C. and Towne, E. B.: “Bacteriological observations in experimental poliomyelitis of monkeys.” Med. Res., 1917, 36, 175-186.
20. Rosenow, E. C., Towne, E. C. and v. Hess, C. L.: “The elective localization of streptococci from acute poliomyelitis.” Infect. Dis., 1918, 22, 313-344.
21. Rosenow, E. C., Towne, E. B. and Wheeler. G. W.: “The etiology of epidemic poliomyelitis: Preliminary notes.” Arn. Med. Assn., 1916, 67, 1202-1205.
22. Wickman, I.: Acute poliomyelitis. trans. New York, Jour. Nervous and Mental Dis. Publ. Co., 1913, 135 pp.