UNDULANT FEVER IN BOMBAY*

By L. MONTEIRO, mj>.

and

J. C. PATEL, M.D., ph.D., M.R.C.P.

K. E. M. Hospital, Bombay

Undulant fever is not confined to the small island of Malta where it was first recognized but is known to occur all over the world. It has been reported from North and South

America, England (Cruickshank and Barbour, 1931; Wade, 1933), from various parts of Europe particularly Denmark; from China, the Philippine Islands, Africa and Australia. It has also been

reported from various parts of India : from the

Punjab (Bardhan, 1943), from South India

(Pandalai and Raman, 1941), from Bengal (Chaudhuri and Rai Chaudhuri, 1943) and from Bombay (Vaidya, 1939; Joslii, 1944). This paper is a summary of proved cases of

the disease admitted to the various hospitals of Bombay and studied in the course of the last three years. Age and sex.?In this series of nine cases the

youngest was a girl of 11 and the oldest a man aged 60 years, the rest ranging from 18 to 42

years which is the susceptible age period for undulant fever. Six were males and the rest females.

Occupation.?Occupation plays a definite role in the aetiology of the disease because of the

opportunities it provides for infection. Of the nine cases one was a cleaner of hides in a tanning factory, one a butcher, one a salesman in a

milk shop and one attended a ewe during an abortion. In the rest the nature of their

occupation did not seem responsible for the infection. Three cases (nos. II, VII and IX) contracted

the infection through skin contact and one case (no. VIII) by drinking the milk of a ewe which had aborted. In the rest of the cases the infec- tion was presumably conveyed through milk taken raw. Cases nos. VIII and IX are examples

* A paper read before tlie meeting of the Association of Physicians of India held in Bombay in April 1946.

Dec., 1946] UNDULANT FEVER IN BOMBAY : MONTEIRO & PATEL 509

of infection occurring in the same family the first by drinking raw milk and the other by skin contact. As regards the communal incidence six were

Hindus, two Muslims and one Christian. Residence.?Five out of the nine cases came

from Kathiawar and Cutch (Western India). The cases reported by Vaidya (1939) and the one of Joshi (1944) were also from Kathiawar. ft would seem that brucellosis is quite prevalent in Kathiawar. Cases nos. I, II and VII came lr?m the suburbs of Bombay.

Table I

Case number

I II III IV V VI VII VIII IX

Age

42 18 26 11 36 30 40 60 30

Sex

M. M. M. F. M. F. M. M. F.

Religion

Ch. H. H. M. H. H. M. H. H.

Place

Bandra (Bombay) Bombay Nasik Kathiawar

Ivurla (Bombay) Cutch

Mode of infection

Hog contact milk Tanner (contact) Milkman Milk

Butcher Milk Contact

Month

October April October January October November

September November

August

Seasonal incidence.?Seven cases out of nine started getting fever between the months of August and November (table I). Case no. II 'the tanner) contracted the fever in April and no. py in January. This August to November period is noteworthy, as it is the calving season for cattle in India generally and the period of increased production of milk. The contamina- tion of the milk with brucella organisms will

therefore be more marked during this season,

fn various other countries where undulant fever prevalent, the highest incidence coincides with

the calving or kidding season, the season in ^ hich large quantities of milk are produced.

. Clinical symptoms and signs.?Prolonged con- tinuous fever was the main symptom in all the cases. In the majority of them, the fever was continuous in the first month and the undulations became evident in the third month of the disease. The longest duration was twelve Months and the shortest three months. Loss of height occurred in five out of nine cases; it was marked in three cases. In spite of the high fever Persisting for months the patient hardly looked JU and two of them continued to do light work. Chills occurred in four cases and two of them complained of profuse perspiration. There were lew physical signs. The spleen was palpable in five cases and there was bronchitis in two cases. The liver was palpable in two cases. Arthritis

find rheumatic pains in the joints were present ln cases nos. II, VI, VII, VIII and IX. Laboratory diagnosis.?A clinical diagnosis brucellosis is no easy problem in view of the

occurrence of atypical and subclinical infections. If this condition is kept in mind, especially in cases of pyrexia of obscure origin, a larger number of cases may come to light. A definite

conclusion can, however, be arrived at only by a bacteriological examination.

In the present series, the diagnosis was made when the fever had lasted for more than two months. Till then, the investigations and treat- ment postulated malaria, typhoid or tuberculosis. Only when the fever failed to respond to anti- malarial drugs, and laboratory examinations for the enteric group of organisms and tuberculosis were negative, was the possibility of undulant fever envisaged. The first investigation that

pointed the nature of the disease was the

agglutination test. This, as mentioned before, was carried out well-nigh two months after the onset of the disease, at a time when the

agglutinins in the blood would be present in a suggestive titre. The test was carried out

against standard Oxford suspensions of B. abortus and B. melitensis. The highest titres obtained varied from about 1 in 500 to 1 in 3,500. In some cases differentiation as to. the type of infection could not be arrived at from these results. Table II shows the various titres obtained. Agglutinin absorption tests with serum obtained from patients were not carried out. Such high titres are rarely met with, except as a result of active infection, and in

clinically suspected cases is strong evidence in favour of brucellosis. In two cases where the blood culture was negative the diagnosis depended' on the agglutination test alone. It must be emphasized that a negative agglutina- tion reaction is possible even during the active phases of the disease and for a comprehensive study the isolation of the causative organism becomes imperative. The organism can be isolated most frequently

from the blood. Blood culture was carried out in all the cases. As will be seen from table II

organisms belonging to the genus Brucella were grown in seven cases out of the total of nine.

The blood was collected at the height of the fever, if present, or after a provocative milk injection. Ten ml. of blood were inoculated in Hartley's broth and incubated under ordinary atmospheric conditions. Growth was observed about a week

later, subculture being made on nutrient agar and the morphological and cultural characters studied. Biochemical reactions showed no fermentative activity with the usual carbohydrate

510 THE INDIAN MEDICAL GAZETTE [Dec., 1946

Table II

Case number

I

II

III IV

V VI VII VIII IX

Agglutination titre of

SERUM AGAINST STANDARD

SUSPENSIONS

Br. melitensis

Not done

9f

2,000

2,000 400

2,000 1,000 500

Br. abortus

500 2,000 500

1,000 1,000 1,000 1,500

2,000 400

3,500 2,000 1,000

Blood culture

Positive

No growth Positive

No growth Positive

h2s

+ ve

+ ve

+ ve

ve

+ ve ve

ve

Antigenic structure mono- specific Oxford sera

Br. abortus

25 complete 50 incomplete 100 complete 200 incomplete

50 complete 100 incomplete

125 125 125 50 complete 125 incomplete

Br. melitensis

25 complete 50 incomplete 50 complete 100 incomplete

50 complete 100 incomplete 50 50 25 25

Classification of organism

Probably Br. abortus.

Br. abortus.

Probably Br. abortus.

Br. melitensis ? Br. abortus. Br. abortus ? Br. abortus ?

substrates. The production of hydrogen sulphide (H2S) was observed for at least seven days. The organisms were tested against mono-

specific Oxford sera. Table II shows the results. All the serological reactions were

carried out soon after the isolation of the

organism, in their smooth phase, before a change of the antigenic structure to a rough form could occur.

The classification and identification of these

organisms is difficult because of the subtypes of the related types. The criteria usually used in the differentiation of the various types are the C02 sensitivity at primary isolation, growth in the presence of dyes, H2S elimination, the antigenic structure and the virulence test. All the strains in the present series were isolated after incuba- tion in air without an increased C02 tension. It was observed that the growth in the primary cultures was slow, taking a week or more to

appear. It is conceivable that the small amount of C02 present after inoculation of the medium and the burning of the plug was sufficient to initiate the growth, the C02 requirements sub- sequently being supplied by the growing organisms themselves.

Cultivation in the presence of dyes to test their inhibitor^ activity gave equivocal results and was not persisted with. Inability to obtain the standard dyes may have been responsible for these results. Virulence tests were not attempted in any of the cases. An analysis of table II reveals several interest-

ing features. It will be seen that, out of the total of seven strains, only two can definitely be placed as Brucella abortus (cases nos. II and VII). Cases nos. I and IV showed cultural characters of Br. abortus, though antigenically the results were not conclusive. Case no. VI, though culturally resembled Br. melitensis, antigenically belongs more to the abortus variety. Cases nos. VII and VIII, where contact has been with sheep, antigenically resemble

Br. abortus, though H2S was not produced. These results have been very confusing, but as mentioned at the beginning of this section, the existence of subtypes is probably responsible for this state of affairs. Not all varieties of Brucella abortus require

the presence of increased C02 tension during primary isolation. The Southern Rhodesian

variety (Topley and Wilson, 1946) is an example. Again there have been strains isolated in S. E. France (Topley and Wilson, 1946) which, though they show the biochemical characters of Br. melitensis, possess the antigenic structure of Br. abortus. The animal source of origin may be extremely

helpful, especially as the above investigations are not very conclusive. Polding (personal communication, 1946) working on brucellosis, at the Imperial Veterinary Research Institute, Mukteswar, India, finds in a total of 49 strains studied, 26 Brucella abortus, 3 Br. melitensis and 20 unclassified strains. Of the three melitensis strains, one was obtained from a cow, one from a goat and one from a human source. The rest of the strains were all obtained from

cows, buffaloes and one from a horse. The unclassified strains gave ambiguous results, among other characters the ability to grow in air at first isolation, the production of H2S, and antigenic instability. The larger number in his series were abortus and the smaller number

melitensis, serological differentiation not being as sharp as in the standard strains. This unclassi- fied group has been called the aberrant variety and is indigenous to this country. The doubtful strains in our series, therefore,

could correspond to the aberrant variety de- scribed by Polding or to some other subtype. A fuller investigation on a larger number of strains should throw some light on the occurrence of indigenous variants in this country. The third type of brucella organism, Br. suis,

responsible for some cases of the disease in

J

Dec., 1946] UNDULANT FEVER IN BOMBAY : MONTEIRO & PATEL 511

America and Denmark, antigenically and bio-

chemically related to Br. abortus, cannot be

differentiated from this organism. The dye tests, the animal source and the country of

origin are useful. No cases of infection by Br. suis have so far been reported from India.

|n the present series, there is one case in which

there has been contact with hogs (case no. I),

"^here the infecting organism is probably Br. abortus.

It is well known that the three main types, Br. melitensis, Br. abortus and Br. suis produce 'he disease in goats and sheep, cattle, and hogs

respectively. Interchangeability of the host is

known to occur either as a result of contact or

under experimental conditions. The occurrence

Brucella abortus type of organism in sheep (cases nos. VII and VIII) may, therefore, be

accountable. In India, several workers have reported cases

?t# brucellosis. In some of these cases, the

etiological agent has been isolated. This has

jn every instance been Br. melitensis, a contrast

to the present series. Treatment.?Most of our cases were treated

symptomatically before the diagnosis was

established and all of them unsuccessfully with

Yv\ln*ne an<^ niepacrine in the early stages. Vhen the fever still persisted, they were treated

as enteric infections. Once the diagnosis of

undulant fever was proved an adequate diet was given. This series was treated with sulphona- nndes. This was completely successful in three cases and curtailed the length of bouts in others, n case no. I sulphaguanidine was given con-

J?U0usly in a dosage of 8 gm. a day for ten days.

he fever settled down on the fourth day and 1

gained normal afterwards. After an interval of seven days sulphaguanidine was repeated in

he same dosage for eight days. The fever never

^curred. In cases nos. VIII and IX sulpha-

^ azine in a daily dosage of 4 gm. brought the

emperature down to normal on the sixth day and has remained normal since then. Sulpha- tiiazine was given in these cases consecutively lQr eighteen days. In case no. VII, 9 gm. of

^nlphamerazine was given daily for 18 days, i.e.

a total of 187 gm. The temperature settled Uown to normal on the sixth day and remained so for one month. There was a relapse and

consequent readmission during which period the ganism was again isolated from the blood.

. wphamerazine was again successful in curtail-

lng the relapse. In cases where sulphona- mides were administered, blood was frequently examined to check its level and the effect

on the

cytological element. Bardhan (1943) reported the curative effect of the drug in cases which

he

treated in Lahore. Debono (1939) on the other hand pronounced them ineffective in a series of

cases of undulant fever in Malta. Horn

(1940) found them exercising a favourable

influence on the subjective symptoms of the

disease. On a review of literature available and

r?m personal experience of the above cases it

can be reasonably concluded that sulphonamides are not specific in the treatment of undulant fever. They do however abort the bouts of fever and thus shorten the period of relapse undulation. Chaudhuri and Rai Chaudhuri (1943) came to similar conclusions. Other drugs were not tried in this series. Mode of infection and infecting organism.?

In case no. II (tanner) and case no. VII (butcher) the infection was obviously contracted through the skin while handling a brucella infected carcass or meat. Case no. IX got infected through handling the afterbirth of the ewe which had aborted and case no. VIII by drinking raw infected milk of the same animal. In both of these cases the infecting organism was probably Br. abortus. It is known that

sheep carry Br. abortus infection. The remain-

ing four cases (three from Kathiawar and one from Nasik) probably developed infection by drinking raw milk of cattle or sheep. In the fourth the organism was not isolated. In the case from Bandra (case no. I) the source of infection could not be ascertained but was

probably with milk or contact with hog. The type of organism.?Br. abortus or its

aberrant varieties were isolated from six out of seven positive cultures. This fact suggests cattle (cow and buffalo) rather than goat to be the source of infection. Cattle in India are

known to carry Br. abortus infection and so also

may Indian sheep by contact with infected cattle. In parts of America where cattle breeding is

common Br. abortus infection is more pre- dominant than Br. melitensis. In England, too, Br. abortus is much commoner than

Br. melitensis infection, so much so that 95 per cent of undulant fever there is ascribable to

Br. abortus. Out of 49 strains of Brucella studied at Mukteswar the majority were of Br. abortus variety or its Indian aberrant types. In India only a negligible quantity of goat's milk is consumed and that too only by shepherds. Milk in general use is from the buffalo, the cow and to a slight extent from the sheep. In certain

parts of the country raw milk is habitually drunk from a common belief that raw milk is more nutritive. A possible source of infection

may thus be the milk from infected cattle and

conceivably undulant fever may be more wide- spread in our country than is generally realized. This is probably even more true for the rural

than the urban areas.

Kristensen (1928), commenting on the high incidence of Brucella abortus infection among the population of Denmark, stated

' there is no

reason to believe that this infection is more

widespread here in Denmark than in other

countries where cattle breeding is carried on to

some extent. It must be supposed that if

systematic inquiries of a similar nature were set on foot in Germany and England the same condi- tion would be found'. India owns one-third of the cattle of the world, and there is no reason why Kristensen's remarks should not apply

512 THE INDIAN MEDICAL GAZETTE [Dec., 1946

to this country. By co-operation between

physicians, veterinary surgeons and public health (milk) authorities, the sources and pre- valence of infection wquld, it is suggested, be probably detected earlier.

Summary

1. Nine cases of undulant fever are reported. Seven diagnosed by isolation of the organism and two by agglutination test.

2. The source and mode of infection of these cases are discussed.

3. The treatment of undulant fever with

sulphonamides is described. The results are not

encouraging. We thank the Dean and the Physicians of K. E. M.

Hospital for allowing us to investigate, treat and report some of the cases. Dr. B, M. Amin was responsible for the isolation of the first two strains. We also thank Drs. B. B. Yodh, M. J. Shah and Jhatakia of Sir H. N. Hospital, and Dr. A. Karamally of Habib Hospital, for permitting us to study their cases. Our thanks are due to Dr. R. Row, Director, P. G. Singhanee Hindu Hos- pital, for allowing us to publish the notes of the last two cases. We are grateful to Dr. C. G. Pandit, Guindy, for his study of the first three strains.

Appendix of Case Notes

Case no. I.?M. R., male, 42, Christian, clerk by occupation, residing in Bandra (Bombay Suburban District), was having a continuous

temperature for nearly 2 months when he was first seen by one of us (J. C. P.) at his residence. There were no physical signs except that he was emaciated and ansemic. The usual investiga- tions like urine, stool and Widal tests were

negative. The total and differential leucocytic counts were normal. He was treated as a case of enteric fever even though the serology was negative. He was allowed a more liberal diet, than he hitherto had, but the temperature con- tinued for another month. He was admitted to the K. E. M. Hospital for investigation on 15th December, 1943. On admission there were no

physical signs except loss of weight and ansemia. The spleen was not palpable. Total W.B.C.s

8,400 per c.mm., the differential leucocyte count was neutrophils 62 per cent, eosinophils 3 per cent, lymphocytes 33 per cent, monocytes 2 per cent; Kahn and Widal tests were negative. Skiagram of the chest was normal. Blood

agglutination against Br. abortus was positive 1

in 500. Organisms of brucella groiip, probably Br: abortus, was grown from the blood. His

temperature settled down and he left the hospital on 30th December, 1943. A recurrence of the fever after an afebrile period of 8 days brought him back to the hospital. Blood agglutination showed a higher titre (1 in 2,000) and the same organism was grown again from the blood. He was treated with sulphaguanidine in the dosage of 2 gm. three times a day for 15 days and it was repeated after an interval of 8 days. There was no recurrence of the fever, and convalescence was uneventful.

There was no contact with any animal except hogs, and the milk consumed by him was from the cow and the buffalo.

Case no. II.?M. S., male, aged 18, Hindu, living in Dharavi (Bombay Suburban District) and employed in a tannery for cleaning hides, was admitted in the K. E. M. Hospital on 27th July, 1944, with a history of continuous fever for 8 days. He had irregular fever for 6 weeks in the hospital and his Widal reaction carried out at intervals of 15 days was thrice negative. There were signs of bronchitis in the chest and the spleen was palpable. The total and differential leucocytic count was within normal limits. On 30th September, 1944, blood agglu" tination against Br. abortus was positive 1 in

5,000 and on 10th October, 1944, increased to 1 in 1,000. Agglutination titre even though examined twice later remained the same. Blood culture taken on 10th October, 1944, grew Br. abortus. He was treated with sulphathiazole which brought the temperature to normal and the patient left the hospital against medical advice. Subsequently he came to the out-

patient department and complained of pain in the joints. His knee, ankle and shoulder joints were swollen and painful for about 8 days. He had two further bouts of fever each lasting for 8 days for which he did not take any treatment.

Case no. VIII.?H. H., 60, Hindu male, was admitted in the P. G. Singhanee Hindu Hospital on 11th December, 1945, with a history of irregular fever and dry cough of one month's duration in Cutch. Physical examination showed enlargement of the spleen, one finger breadth below the costal margin and rhonchi with pro- longed expiration in the chest. The patient was a subject of bronchial asthma. The fever occurred usually in the afternoon without rigors. The patient enjoyed a good appetite. All routine investigations were negative. The tem-

perature did not respond to quinine and atebrin, serum agglutination test was positive for Br. abortus and Br. melitensis, 1 in 1,000. A blood culture taken on 10th January, 1946, was positive. He was treated with sulphadiazine 4 gm. a day. The temperature settled to normal on sixth day of the treatment. He was dis-

charged on the eleventh day with instructions to continue the drug which he did for about 7

days and discontinued of his own accord. There had been no recurrence of the symptoms till July 1946.

Case no. IX.?A Hindu female, aged 30 years, the daughter-in-law of case no. VIII, was

admitted to the P. G. Singhanee Hindu Hospital on 11th December, 1945, with a history of irregular fever for 4 months, cough 2 months and pain in the right side of the chest for 2 months. The fever rose occasionally to 104?F. and was accompanied by chills. On examina- tion there were no physical signs detected except that the patient was pale and anaemic. The usual investigations, including a total and differential count, Widal reaction, urine analysis

Dec., 1946] CERVICAL RIB SYNDROME : MAHMOOD 513

and culture, stool, gastric analysis and a fluoro- scopy of the chest were negative. Agglutination of the blood carried out on 27th Deccmbei, 19 ,

was positive for Br. abortus 1 in 1,000 ana Br. melitensis 1 in 500. A culture of the blood v-'as positive for Br. abortus (?). The treat-

ment consisted of sulphadiazine 4 gin. a day for 18 days.- There had been no relapse till

July 1946.

REFERENCES Bardhan, P. N. (1943) .. Indian Med. Gaz., 78, 535.

Chaudhubi, R. N., and Ibid? 78> 340? Rai Chaudhuri, M. N. (1943).

Cruickshank, R., and Lancet, i. 852. Barbour, W. J. (1931).

. Debono, J. E. (1939) .. Brit. Med. J., t, 326.

Horn, W. S. (1940) .. Texas State J. Med., 36,JJj- (Abstract?/. Amer. Med.

Assoc., 115, 810.) Joshi, R. A. (1944) .. Indian Med. Gaz., 79, 369.

Kristf.nsen, M. (1928). Centralbl. Bakt., 108, 89^ Pandalai, N. G.. and Indian Med. Gaz., 76, 327. Raman, T. K. (1941).

, n , ?

i Topley, W. W. C., and Principles oj Bacteriology Wilson, G. S. (1946). and Immunity. Edward

Arnold and Co., London. Vaidya, R. a. (1939) .. Med. Bull, 7, 75. Wade, E. (1933) .. Lancet, i, 1342.