REDUCTION OF POTASSIUM TELLURITE IN DIPHTHERIA AND OTHER THROAT CONDITIONS

248 Another interesting case with signs resembling mastoiditis was published by Lewis (1919). Reviewing the literature, the disease seems to present itself in two clinical forms : (a) that affecting children, in whom rapidly growing bony tumours and are prominent, and usually called chloroma ; in a that older whom patients, progressive (b) affecting anaemia and signs of leuksemia are more predominant, and usually called chloro-leuksemia. In both types, however, the two essential features of chloroma are present-viz., leubsemic changes in the blood-films and green tumour deposits in bones. Radiologically none of the appearances produced by chloroma in the skeleton can be said to be diagnostic. There may be periosteal elevation with new bone formation laid down in the striae, either parallel Osteoor perpendicular to the shaft of the bone. porosis may either be generalised, or it may be seen as pin-point areas of destruction, as larger punchedout areas, or as erosions near the ends of the diaphyses. There are no changes in the epiphyses-a feature which distinguishes the condition from scurvy and rickets. Similar radiographic appearances to those of chloroma may also be produced by leuksemia, more especially the lymphatic variety, and by other bone diseases-namely, Ewing’s tumour, osteogenic sarcoma, carcinomatous deposits, myelomata, sarcomata, congenital syphilis, and Hodgkin’s disease. The disease is always regarded as fatal. The average duration is about 6 months, but cases have lasted as long as 18 .months. No effective treatment is yet known. Irradiation with deep X rays and radium have yielded no success, and appear to make the condition even worse. Drug therapy has produced equally bad results. Blood-transfusions only produce temporary benefit and do not stem the pathological process. Nevertheless two recoveries are recorded in the literature. In the case described by Lecene (1927) a green tumour was excised from the humerus and reported on as myelocytic chloroma, though the blood-count was normal. This was followed by deep X-ray therapy and the patient was reported to be alive and well 2 years later. Washburn (1930) described a case in a boy aged 22 months. A green tumour was excised from the skull and reported upon as a myelocytoma. Another tumour was present in the femur, and the blood-count was reported on as doubtfully leukæmic. Deep X-ray therapy was given. After treatment the blood was said to be normal. The patient was well 2! years later. In neither of these cases does the diagnosis of chloroma seem to be strongly established, for the usually accepted criteria do not seem to have been fully satisfied. In both cases green tumours were described, but in Lecene’s case the blood was almost normal, and in Washburn’s patient the blood-films were not very definitely leuksemic. SUMMARY

A typical case of chloroma is described in a young adult. The condition is rare, less than 200 cases having been reported since 1821. It is characterised by (a) the appearance in bones of green tumours composed of myeloblastic cells which infiltrate the tissues like malignant disease, and (b) a blood-picture resembling myeloblastic leuksemia. Tumour formation is the most prominent feature in children and progressive anaemia in adults. The disease is usually fatal within 18 months. I wish to express my thanks to Dr. Herbert T. Evans for his permission to publish this case ; to the staff of the department of pathology of the Welsh National School of Medicine for the post-mortem

details and the photomicrograph ; Marjorie Bryan, the house-physician her help with the clinical notes.

and to Dr. of the case, for

BIBLIOGRAPHY

Askanazy, M. (1917) Int. Clin. 1, 37. Bamforth, J., and Edwards, J. L. (1933) Lancet, 1, 857. Boots, R. H. (1917) J. Lab. clin. Med. 2, 622. Brannan, D. (1926) Bull. Johns Hopk. Hosp. 38, 189. Burgess, A. M. (1912) J. med. Res. (n.s.) 22, 133. Burns, A. (1823) Observations on the Surgical Anatomy of the Head and Neck, Baltimore, p. 386. Critchley, M., and Greenfleld, J. G. (1930) Brain, 53, 11. Dock, G. (1893) Amer. J. med. Sci. 106, 152. and Warthin, A. S. (1904) Med. News, N.Y. 85, 971. Doub, H. P., and Hartman, F. W. (1935) J. Amer. med. Ass. 105, 942. Huber, K. (1878) Arch. Kinderheilk. 19, 129. Jacobaeus, H. C. (1909) Dtsch. Arch. klin. Med. 96, 7. Kandel, E. V. (1937) Arch. intern. Med. 59, 691. King, A. (1853) Mon. J. med. Sci. 17, 97. Lecene, P. (1927) Bull. Soc. nat. Chir. 53, 1328. Lehndorff, H. (1910) Ergebn. inn. Med. Kinderheilk. 6, 221. Lewis, E. C. (1919) Lancet, 2, 830. Meyer, P., and Berger, L. (1924) Arch. Mal. Cœur. 17, 39. Pissavy and Richet, C. (1912) Ibid, 5, 248. Rothschild, H. (1926) Dtsch. Z. Nervenheilk. 91, 57. Simon, W. V. (1912) Berl. klin. Wschr. 49, 893. Washburn, A. H. (1930) Amer. J. Dis. Child. 39, 330. —

REDUCTION OF POTASSIUM TELLURITE IN DIPHTHERIA AND OTHER THROAT CONDITIONS *

BY K. E.

COOPER, Ph.D. Leeds, L.R.C.P., A.I.C.

SENIOR BACTERIOLOGIST

MEDICINE,

IN THE DEPARTMENT OF PREVENTIVE UNIVERSITY OF BRISTOL

B. A. PETERS, M.D. Camb., D.P.H. SUPERINTENDENT OF THE INFECTIOUS HAM GREEN, BRISTOL ;

DISEASES

HOSPITAL,

AND

J. WISEMAN, B.SC. Edin., AND J. M. DAVIES, B.Sc. Edin, ASSISTANT BACTERIOLOGISTS IN THE DEPARTMENT OF PREVENTIVE MEDICINE, UNIVERSITY OF BRISTOL

THE announcement of the possibility of more rapid diagnosis of diphtheria (Lancet, 1938) is always sufficiently important to demand investigation into the accuracy of the methods suggested. Dr. Alfredo Manzullo (1938) claimed that if a 2 per cent. solution of potassium tellurite, not more than a month old, were painted on the white exudate on the tonsil of a patient suffering from diphtheria, the membrane blackened within fifteen minutes-owing to reduction of the tellurite-but that no change took place in similar conditions such as streptococcal tonsillitis. He also claimed that a rapid bacterial diagnosis could be made in vitro by incubating a swab in a special liquid tellurite medium for three hours and observing black colonies on the swab in cases which were due to diphtheria, or the failure to produce any blackening in cases that were not. We have compared the results of the in-vivo test with the clinical and bacteriological findings in a series of 84 cases and the results of the in-vitro test with the bacteriological findings in a series of 277 swabs. A swab (taken before the in-vivo test was made) was inoculated on the Löffler’s medium, then on to a McLeod’s tellurite plate, and then subjected to the in-vitro test. The bacteriological findings were obtained without a knowledge of the result of the in-vivo test, which was made by one of us (B. A. P.) along with the clinical observations. The result of the in-vitro test was recorded for each swab before a bacteriological diagnosis had been made and in the absence of clinical knowledge of the case. All strains isolated on McLeod’s tellurite were typed according *

Based

on a

paper read at the on July 8.

Pathological Society

Birmingham meeting of the

249 to his classification (Cooper et al. 1936). Any case forms from L6ffier when stained by Neisser, which failed to appear on the tellurite plate, was subcultured from the Loffier to tellurite and the strain isolated investigated to see whether it was diphtheria or a diphtheroid. (Only 9 such swabs appeared in the 277 examined, and from 4 of them diphtheria was isolated. The other 5 were apparently

giving granular

Such results have been discolorations appeared. separated from the definite ones and called doubtful; they have been excluded from table III entirely. As regards nasal swabs, such reactions were usually on swabs which proved to be negative for diphtheria, TABLE II—IN-VITRO

TELLURITE TEST

diphtheroids.) THE IN-VIVO TEST

Table I gives the results of the in-vivo test comwith the clinical and bacteriological findings. pared " Severe " cases mean cases with extensive membrane and oedema of the neck in which the clinical diagnosis was certain. " Moderate " cases are those with well-marked membrane but no oedema of the neck. "Doubtful" cases include cases of follicular tonsillitis with patches of exudate, 1 case of Vincent’s angina, and 1 case of agranulocytic angina with white sloughs on the tonsils. In 57 cases where Corynebacterium diphthericu was found 55 were intermediate, 1 gravis, and 1 mitis. TABLE I-IN-VIVO

TELLURITE TEST

but as regards throat swabs they were more numerous and an equal percentage of bacteriologically positive or bacteriologically negative swabs gave doubtful

reactions.

Manzullo claimed accuracy for this method only

regards throat swabs and said that nasal swabs did not give satisfactory results. Table II shows that 68 per cent. of bacteriologically positive nasal swabs are negative by this test. With throat swabs on the other hand, 88 per cent. of bacteriologically positive swabs gave some darkening. This suggests that factors other than the presence of diphtheria organisms are necessary for the reduction of tellurite. Swabs soaked in pure cultures of diphtheria give no reduction by the test. Preliminary experiments reported by Manzullo suggest that fibrin may play a part in the reduction. The results on positive throat swabs do not in themselves suggest that the test is without value, but table II shows that baoterioas

In the 25 severe cases in which the clinical diagnosis certain there were 6 negative in-vivo tests. In 2 other cases we failed to grow 0. diphtherice although the in-vivo test was positive. We have not infrequently observed with this type of diphtheria that the original throat swab may be negative and may be followed later by a positive swab. In 27 out of the 28 moderate cases C. diphtherice was isolated, and 5 of these gave negative in-vivo tests. Therefore, out of 52 definite cases of diphtheria, the in-vivo test failed in over 20 per cent. of cases. Of the 8 doubtful cases in which C. diphtheriœ was recovered 3 gave negative in-vivo tests. It might be that in these cases this organism was not the real pathogen. A more noticeable feature of this group was the number of false positives-15 in which no 0. diphtherice could be recovered. Of the 15, 4 were scarlet-fever cases with patchy tonsils, 1 Vincent’s angina, 1 agranulocytic angina, and 9 follicular tonsillitis. If all the cases in which C. diphtheriœ was recovered are included, the in-vivo test gave 13 false negatives out of 57 bacteriologically proved cases. In the 27 cases in which this organism was not recovered the in-vivo test gave 17 positives, and probably 15 of these were false positives. With such a high percentage error in both directions, it is doubtful if the test is of any great value. was

THE IN-VITRO TEST

The results of the comparison of the in-vitro test with the bacteriological findings are shown in table II. In the results on 100 cases Manzullo (1938) does not include any doubtful reactions. We have found difficulty in several cases in deciding whether his test was positive or negative, for indefinite grey

swabs also give a positive test in 34 per cent. of cases and a doubtful result in a further 21 per cent. It thus seems probable that the reduction depends not so much on the presence of diphtheria

logically negative

TABLE III—IN-VITRO

TELLURITE TEST DOUBTFUL

(EXCLUDING

RESULTS)

I

I

on the swab but of organisms plus some additional factors, which are yielded by throats subjected to certain types of inflammatory reaction. We hope to publish investigations now proceeding to determine the factors responsible for this reduction. Manzullo says that after reading the results of the in-vitro test, they are confirmed by making films and staining by Gram’s method. We have found it impossible to distinguish C. diphtheriœ from the diphtheroids usually present under these conditions. The films showed an abundance of pleomorphic organisms, and we found no certain distinction between bacteriologically positive or negative swabs. Some of the swabs giving most reduction of tellurite showed an abundance of fusiform bacilli and spirochætes, suggesting that anaerobic conditions were established during the three hours’ incubation, despite the fact

organisms

250 that the position of the swab provided for maximal
the

.