Paratyphoid C. in British Guiana

285 TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE. Vol.XXIII. No.3. November,1929.

COMMUNICATIONS. P A R A T Y P H O I D C. IN B R I T I S H GUIANA. CLINICAL AND EPIDEMIOLOGICAL NOTES. BY

GEORGE GIGLIOLI, M.D. (ITALY), D.T.M. & H. (LONDON), Chief Medical Officer, The Demerara Bauxite Co., Ltd.

In a paper published elsewhere (GmLIOLI, 1929) I described the steps which established that a prolonged pyrexia, frequently observed among patients from the Demerara River district admitted to the hospital of the Demerara Bauxite Company at Mackenzie, was paratyphoid C. I recognised the condition as a clinical entity in 1923, referring to it, tentatively, in my annual report as " intestinal fever." The clinical description of the disease given here, however, is based upon ninety-two cases in which tile diagnosis received laboratory confirmation. I.

CLINICAL DESCRIPTION. INCUBATION.

No conclusive data were obtained to determine the length of incubation of the diseases, in all cases the exact source of the infection was unknown. Considering the chronologicalsuccession of cases in the single locality, intervals of from a few days to one month or more were noted (vide " VI. Epidemiology "). Such data are of only relative utility as regards incubation since the infectivity of a patient lasts for considerable time, and they fail to take into consideration light or abortive cases the majority of which escape observation and which are without doubt the most dangerous means of spread of the disease. ONSET.

Some cases give a history of several days of general malaise ; more often the fever starts suddenly, with marked headache, lumbar and joint pains, and

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PARATYPHOID C, IN BRITISH GUIANA.

alimentary, mucous or bilious vomiting. Epistaxis was noted in three cases. The possible influence on this sudden mode of onset of a concomitant malaria infection must be considered in a high proportion of cases. (Chart 2.) TEMPERATURE CURVE.

Paratyphoid C. is eminently a " fever," and its temperature curve constitutes its most characteristic symptom in spite of very considerable variability. It is typically a daily remittent or intermittent temperature ; the fastigium varies from 100 ° F. to 105 ° F., and usually occurs in the afternoon. In a few cases a double fastigium is observed in twenty-four hours. T h e temperature falls during the evening and night often with profuse sweating, and is normal or nearly so in the morning. More rarely the fastigium may occur in the morning and defervescence in the afternoon. These characters are best seen in the protracted cases lasting twenty to forty days (Charts 1 and 2). The daily rise of temperature may be accompanied by a slight chili, headache is constant, pains i n the joints and lumbar regions are common. In the protracted cases one frequently notes a marked irregularity in the temperature c u r v e ; the temperature falls to normal, or nearly so, for several days, to rise again to 103 ° F. or 104 ° F. CHART NO. 1. ~,,.t~,, ~ ~

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T h e end of the febrile stage may be reached gradually by lysis, with a progressive fall of a half to one degree daily in the afternoon rise of the temperature. Not rarely it is abrupt, the morning fall to normal not being followed, as usual, by a rise in the afternoon. Chart No. 1 refers to a typical mild case with a daily intermittent fever ; with the exception of one day the morning temperature was normal during the whole period of observation. Chart No. 2 refers to a serious protracted case lasting thirty-eight days, and ending favourably; of thirty-one days of observation the morning temperature was normal in eighteen. T h e same remittent or intermittent curve is found in cases of short duration, from three days to two weeks. M u c h more rarely the temperature may remain

GEORGE GIGLIOLI.

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persistently high with only slight remissions ; in such cases the lungs are usually involved, and secondary infections dominate the scene. 9.s 19..~ l ~ o I.a-, I,'a~ I ~

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CHART NO. 2. Temperature curve from a case of paratyphoid C. complicated with benign tertian malaria in a 20-year-old negro, admitted on the seventh day of disease : h~emoculture positive on the seventh and twenty-seventh days ; P . v i v a x present in the blood. Typical protracted case lasting thirty-seven days, with deeply remittent temperature curve. Note the modification of the curve during the first three days caused by the double infection and disappearing after quinine treatment. Recovery. CHART NO. 3. Temperature tO.~

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PARATYPHOID C. I N BRITISH GUIANA.

and difficulty may be experienced in persuading t h e m to remain in hospital and in bed. L a d d e r - s h a p e d curves are frequent ; Chart No. 3 is a good example of an ascending ladder, the fastigium occurred in the morning and defervescence in the afternoon with profuse cold sweats and algid symptoms. T h e patient was delirious throughout, and died in collapse on the fifth day of observation. Descending ladders are commoner, more characteristic, and often associated with the most desperate cases. Charts Nos. 4 and 5 are good examples, and both refer to fatal cases. Death in an apyretic condition is frequent (Charts 4 and 5). In infants the same remitting or intermitting character is found in the temperature curve. In fatal cases both a ladder-like fall with collapse, and a ladder-like rise with hyperpyrexia and convulsions, have been noted.

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CHART NO. 4. Temperature curve from a case of paratyphoid C. in a 25-year-old negro, admitted on the fourth day of disease : note the fall of the temperature on the fourteenth day, in spite of persistent serious nervous symptoms : delirium, intractible hiccough and progressive decline leading to death in a deep astenic condition on the twenty-first day. PULSE.

DissociatiolI of the pulse rate and temperature is frequent ; rates of 92 and 100 with temperatures of 104 ° F. have been observed. In serious cases, as in those with continuous high temperature and involvment of the lungs, persistent rates of 120 and more are common. A progressive ladder-like fall of temperature, accompanied by a progressive increase in the pulse rate to 140 or 150, is a frequent s y m p t o m of very grave prognosis. In algid cases, the pulse

GEORGE GIGLIOLI.

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GENERAL APPEARANCE.

There is nothing characteristic in the majority of the mild cases, even if of long duration. The appearance of the patient is unusually good. In serious cases, the sunken eyes and anxious delirious expression contrast with the classical apathetic listless appearance of serious typhoid fever cases. GASTRO-INTESTINAL SYMPTOMS.

The tongue is not characteristic. In mild cases a thin white or yellowish coating is found ; in serious and advanced cases the tongue may present a brown, parched, cracked surface. The apex, margins and papillae, show no special alterations. Vomiting, often bilious, is a very frequent prodromal s y m p t o m ; it rarely continues when the disease is established. It is constant in cases in which paratyphoid C. and malaria co-exist. H~ematemesis was noted in one case a few hours before death. In another fatal case the stomach was full of coffee-ground matter after death. Abdominal pain is frequent during the early part of the disease. Intestinal symptoms are conspicuous by their absence. In a series of seventy-two cases, bacteriologically confirmed, forty-three showed a perfectly norma] intestinal function ; seven were slightly constipated, and eighteen had diarrhoea at the time of admission. The latter condition persisted throughout the disease*in one case, in the remainder it cleared up from the second to the fourth day after admission, and was constantly related to the abundant use of purges before entrance to hospital. The stools were plain, watery and brown. In a further series of thirty-four cases in which the diagnosis

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PARATYPHOID C. IN BRITISH GUIANA.

was only clinical, twenty-five had a normal bowel function, seven were constipated, two had a transitory diarrhoea on admission. H~emorrhage from the bowel was not observed. A small amount of coffeeground material was found in the bowel in some instances after death. In infants, the disease appeared nearly constantly associated with the passage of green mucous stools, identical with those of summer diarrhoea. The liver was enlarged, usually passing the costal margin by one or two finger-breadths ; it was often slightly tender ; a subicteric tinge of the sclerm was common ; marked jaundice occurred in the majority of fatal cases during the terminal stage. Bilious vomiting has already been mentioned. RESPIRATORY SYSTEM. Epistaxis was noted in three cases, as a prodomal symptom. With the exception of the very slight, abortive cases, slight diffuse bronchial symptoms were the rule ; fine crepitant rales were present particularly over the lower lobes. Cough was usually present, sometimes persistent, troublesome, and with abundant muco-purulent expectoration. In the majority of rapidly fatal cases, the involvement of the lungs was much more important, with distinct basal broncho-pneumonic symptoms. In three cases, the whole clinical picture, as also the appearance of the lungs after death, was typical of lobar pneumonia, with persistent high temperature and characteristic rusty sputum. In these cases, the diagnosis was made postmortem, the unusual appearance of the spleen requiring cultures to be taken. Bacillus paratyphosus C. was grown in pure culture. Smears from the sputum showed abundant staphylococci, streptococci and pneumococci. Isolation of B. paratyphosus C. from the sputum was attempted in two cases, but failed. CIRCULATORY SYSTEM. No special symptoms were noted during the onset and course of the disease. The characters of the pulse have been described. Heart failure with dilatation of the right cavities was a characteristic terminal feature in fatal cases. THE SPLEEN.

This was constantly enlarged. Usually,the lower pole reached the anterior axilIary line, or could be palpated at the costal margin ; in one case the lower pole passing the umbilicus. The organ was tender, sometimes painful. The possible influence of co-existingmalaria must again be considered. But there is no doubt that enlargementof the spleen is a constant symptom of paratyphoid C. infection, though its degree is very variable. GENITO-URINARY SYSTEM.

Albuminuria was present in 60 per cent. of cases, the amount varying from a

GEORGE GIGLIOLI.

241

trace to ½ or 1 per thousand. Sugar was absent. Biliary pigments were frequently present. In most cases the urine was clear, often with fine light flakes in suspension. In many a few leucocytes and scarce hyaline and granular casts were noted. In a few the urine was cloudy, gave an abundant sediment, with a large number of white cells, hyaline and granular casts, and very numerous caudate cells from the pelvic epithelium. B.paratyphosus C. was easily obtained in all cases in which culture was attempted during the course of the fever. B. coli was also constantly present, and was frequently cultivated from the renal pelvis after death. The diazo reaction and Russo's methylene blue reaction were positive, but similar results were obtained in patients suffering from other diseases, and in healthy controls. NERVOUS SYSTEM.

Headache was constant, restlessness and delirium very frequent in severe cases, the latter often of a wild type requiring careful watching and restraint. Delirium with apyrexia was frequent. Dysarthria was noted in several instances. Symptoms of meningeal irritation, with convulsions, retraction of the occiput, Kernig's sign, retracted abdomen, vomiting, were twice noted in small children with a fatal issue, and once in a 15-year-old girl who survived. Hiccough was frequent and annoying. In two fatal cases it lasted uninterruptedly for four and five days respectively, resisting all therapeutic attempts, and persisting throughout sleep. Insomnia was frequent. RELAPSES.

The tendency to successive relapses or exacerbations has already been noted in the description of the temperature curve of protracted cases. (Chart 2.) In t w o cases, relapses after periods of thirty and sixty-two days respectively were noted. While in the first the relapse was much more severe than the first attack and ended fatally, in the second it was slight, the fever only lasting three days. In both cases B. paratvphosus C. was isolated by ha~moculture during the relapse. COMPLICATIONS.

Complications of varied nature were noted. main groups :--

These can be classed into two

(A) Complications due to Abnormal Localisation of the Specific Agent of the

Disease. (1) Arthritis.--Two cases of suppurative arthritis of the shoulder joint were noted in infants of 3 and 8½ months respectively. Case 6 4 . - - A male aboriginal I n d i a n of 3 m o n t h s was a d m i t t e d to h o s p i t a l o n t h e 16th April, 1927, w i t h a h i s t o r y of fever every day, a n d g r e e n diarrhoea for t h e past t w o weeks. T h e i n f a n t was m a r a s m i c , w e i g h e d 6 lb. 12 oz. ; t h e skin was dry, scaly a n d w r i n k l e d . H e was passing daily four to six b r i g h t g r e e n m u c o - p u m l e n t m o t i o n s in w h i c h c

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PARATYPHOID C. IN BRITISH GUIANA.

no blood was seen. On the eighth day after admission, immobility of the left a n n was noted ; the shoulder appeared swollen, but only slightly tender. On the following day, the local symptoms having increased, an exploratory puncture was made and pus withdrawn from the joint. Arthrotomy was performed. T h e local conditions improved rapidly, the wound appearing perfectly dry and clean by the second day. General condition continued to get worse ; meningitic symptoms made their appearance with a ladder-like rise of the temperature to t05 ° F. Death supervened on the fourteenth day after admission. Gram-negative, short bacilli were found in smears from the pus obtained from the joint, and B. paratyphosus C. was grown in pure culture.

Case 36.--A male child of mixed race, 8½ months of age, had been repeatedly treated for malaria fever as an out-patient. He was admitted to hospital on 22nd January, 1927, with a history of irregular daily fever during the past three weeks. T h e fever had ceased since a week earlier; during the last two days inability to move the left arm had been noted by the parents. The shoulder joint was found swollen, and the articular capsule distended. Pus was drawn by exploratory puncture. Arthrotomy was performed. T h e child made an uninterrupted recovery, and was discharged on the sixth day, to be treated as an out-patient. Healing was complete by the twelfth day, and function entirely re-established one month after operation. Gram-negative, short rods were found in smears from the pus, and B. paratyphosus C. was obtained in pure culture. I n one i n s t a n c e a l~lain serous arthritis of the r i g h t k n e e was o b s e r v e d .

Case 38.--A 21-year-old male negro was admitted on 1st February, 1927, for a daily remittent fever. A fixation abscess was provoked, from which a pure culture of B. paratyphosus C. was obtained. Swelling of the right knee appeared on the twenty-fifth day of the disease, with slight pain. A clear serous exudate was obtained by puncture. The condition rapidly improved with immobilisation and current local treatment. T h e ffmction of the joint suffered no permanent damage, the condition commonly observed in bacillary dysentery. (2) Abscess.--A s p o n t a n e o u s abscess was o b s e r v e d i n o n e i n s t a n c e o n l y , as a p o s t m o r t e m f i n d i n g i n a 4 5 - y e a r - o l d E a s t I n d i a n w o m a n . S h e h a d died o n the d a y of disease w i t h o u t h a v i n g s h o w n signs of r e n a l c o m p l i c a t i o n s . A t a u t o p s y b o t h k i d n e y s s h o w e d n u m e r o u s r e t e n t i o n cysts c o n t a i n i n g a clear fluid. O n t h e left side a s u b c a p s u l a r abscess the size of a s m a l l w a l n u t was f o u n d , w i t h a v e r y w e l l - d e f i n e d r o u n d cavity a n d a f i b r o u s wall. Its c h a r a c t e r s were those of a s u p p u r a t e d cyst. G r a m - n e g a t i v e rods were f o u n d i n the p u s a n d B.paratyphosus C. was g r o w n i n p u r e c u l t u r e . T h e f o r m a t i o n of large fixation abscesses i n the g l u t e a l r e g i o n at the site of i n t r a m u s c u l a r i n j e c t i o n s of q u i n i n e b i h y d r o c h l o r i d e was o b s e r v e d i n t w e n t y cases. T h e i r endogenous n a t u r e was p r o v e d b y the f o l l o w i n g : - (1) B. paratyphosus C. was obtained in many cases by h~emoculture before the administratiqn of quinine by injection. (2) Strict aseptic and antiseptic precautions were observed in the technique of the injections. Parke Davis & Co.'s ampoules were used exclusively. (3) I n no instance were abscesses observed in many hundreds of malaria patients treated by repeated injections of quinine. (4) Formation of bilateral abscesses was noted when the injections had been bilateral. (5) Gram-negative short rods were found in the pus. (6) B. paratyphosus C was obtained in pure culture from the pus in all cases. In no instance were the common pyogenic cocci observed or isolated.

GEORGE

GIGLIOLI.

248

T h e occurrence of abscesses at the site of h y p o d e r m i c or intramuscular injections of various substances has been reported in cases of B. typhosus infection. I n our cases, quinine injection did not invariably cause the f o r m a t i o n of an abscess. Fifty-nine patients suffering f r o m p a r a t y p h o i d C., simple or complicated with malaria fever, received quinine b y intramuscular injection (one to three injections of 10 to 15 gr. each) in the u p p e r and outer q u a d r a n t of the buttock. Of these t w e n t y developed abscesses. O f the thirty-nine who did not develop abscesses fifteen died within five days f r o m the date of admission. Nine died after longer periods ( f r o m six to thirty days), and fifteen recovered without any sign of local complication. T h e interval between the administration of the quinine injections and the appearance of the abscesses varied between five and forty-three days, the average being t w e n t y - o n e days. T h e clinical features of these abscesses are markedly characteristic, and can be s u m m a r i s e d as follows : - (1) The appearance of the local symptoms (abscess) is constantly preceded or accompanied by the fall of the temperature to normal, and a very marked improvement in the patient's general condition, pointing to the onset of convalescence. (2) The evolution of the abscess is afebrile, in spite of very extensive local suppuration, in 75 per cent. of the cases observed. (3) The whole process of evolution of the abscesses is practically painless, and accompanied with no local subjective symptom, with the exception of the appearance of a fluctuating tumefaction on the buttock. Patients affected with large bilateral abscesses will sit up in bed wlthout'difficulty, and not complain of discomfort. In the cases in which the abscesses have been purposely provoked, careful watch has to be kept, as the subjective symptoms are often so slight as to be overlooked by the patient ; the condition might thus continue to evolve to an unnecessary degree, without proper attention. T h e anatomical appearance of the lesions, as noted at operation, is also characteristic. The abscess is situated between the gluteus maximus and medius muscles, extending under the former, in many instances to the median line. In some cases, pus collections are found also among the deeper muscles of the region. No proper limited abscess cavity is found; the pus, which is always very abundant, fills and distends the intramuscular spaces, forming large pockets ; the muscles appear slightly oedematous, of a bright red shiny colour. The pus is watery, of a dirty yellow, of uneven consistency, containing large rag-like fibrinous masses. No odour is noticeable. T h e microscopic examination of smears shows an e n o r m o u s n u m b e r of highly degenerated p o l y m o r p h o n u c l e a r leucocytes. G r a m - n e g a t i v e short and long rods are constantly observed, b u t in varying n u m b e r s : in some cases prolonged search is necessary, in others they are abundant. I n one instance, with m a r k e d tumefaction of the buttock, exploratory p u n c t u r e p r o d u c e d a large a m o u n t of sero-fibrinous exudate, only very slightly corpusculated. T h e exudate became p u r u l e n t in the following days. I n spite of their great extent, these abscesses r e s p o n d rapidly to t r e a t m e n t , and heal completely in f r o m two to three weeks. After incision and drainage

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P A R A T Y P H O I D C. IN BRITISH GUIANA.

of the pus, the w o u n d c o m m o n l y appears quite d r y and clean at the following dressing. I n several cases, while the t e m p e r a t u r e has been normal up to the time of operation, a slight rise m a y develop in the days following intervention. T h i s can easily be explained t h r o u g h the operative trauma, local reabsorption of toxins through the opened vessels, and b y slight secondary exogenous infection. T h e afebrile evolution of suppurative lesions due to B. paratyphosus C. appears to be a v e r y noticeable characteristic ; it was observed not only in these n u m e r o u s cases of abscess, but also in one of s u p p u r a t i n g arthritis of the shoulder in an infant (vide Case 36), and in another of s u p p u r a t i n g cholecystitis. (3) Cholecystitis.--Only one case was registered.

Case 58.--A 19-year-old lad of mixed race was admitted on the 22nd March, 1927, for a daily remittent temperature of seven days' duration. His blood showed a heavy infection with Plasmodium vivax. Quinine treatment by mouth was instituted, and on the second day 15 gr. were administered by intramuscular injection in the buttock. The fever persisted, and on the fourth day B. paratyphosus C. was isolated by hsemoculture. The temperature gradually fell, becoming normal on the twenty-fourth day after admission. An abscess of the buttock became apparent at the site of the quinine injection, and was incised on the thirty-fifth day. Since the fifteenth day the patient had complained of slight pain in the right hypochondrium, and a certain amount of defensive rigidity of the rectus muscle had been noted. Such symptoms persisted with a normal temperature till the fortieth day, when pain became more serious, and a tumefaction became apparent just below the costal margin on the right side ; there was slight cedema of the teguments over this area. There was no jaundice. The patient was passed to the surgical section, and operated upon on the forty-seventh day. A suppurated cholecystitis was found. From the pus, I isolated B. paratyphosus C. in pure culture. T h e complete evolution of this serious suppurative complication, for m a n y days evolving parallel to an extensive deep suppuration of the gluteal region, was absolutely afebrile. (B.) Complications due to Concomitant or Secondary Morbid Conditions. (1) Malaria Fever, mainly of the benign tertian variety, was d e m o n s t r a t e d b y positive blood examination in 29 per cent. of cases. I t is p r o b a b l e that malaria frequently accounted for the sudden onset I have described. T h e t e m p e r a t u r e , which was often high and irregular on admission usually acquired its typical remitting or i n t e r m i t t i n g character after two or three days of quinine t r e a t m e n t (Chart No. 2). T h a t mararia should have had an i m p o r t a n t influence in favouring the epidemic outbreak of p a r a t y p h o i d C. in 1926 and 1927, seems likely, and will be discussed when treating of the epidemiology of the disease. (2) Suppurative Parotitis was noted in one c a s e ; Staphylococcus aureus was present in the pus, and was grown in p u r e culture. (3) Boils were frequent.

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(4) Adenitis of the groin and of the axillary glands with suppuration was noted in two cases, and S. aureus isolated. (5) Bedsores were noted in one case only. (See below, Case No. 77.) In this instance they were very severe, extending to the sacrum, and the patient died on the forty-second day after admission. (6) Pyelonephritis.--The presence of abundant epithelial cells from the renal pelvis in the urinary sediment has been mentioned as a frequent finding. I n one case pyelonephritic lesions were found, and accounted for the fatal termination of the disease. B. paratyphosus C., as we have seen, was present in the urine of most cases ; but B. coli was f o u n d in the pus from this case, and was isolated from the renal pelvis of most cases after death.

Case 77.--A male negro, 22 years of age, was admitted on the 27th August, 1927, with a history of fever since four days. His temperature curve was of the typical daily remittent type, rising to 103° F. in the afternoon ; general condition was poor, the pulse weak and rapid, and the bowels constipated. B. paratyphosus C. was isolated from the blood on the second day. A quinine intramuscular injection was given in order to provoke the formation of a fixation abscess, as the condition of the patient appeared serious. On the ninth day a large bedsore developed over the sacrum. The fever gradually fell and became normal on the nineteenth day, when an abscess of the right buttock became apparent and was incised. The abscess cavity cleaned up rapidly, but the bedsore spread and became deeper extending in depth to the periosteum and bone. Multiple boils developed on the back and limbs; the urine became highly purulent, the patient complained of lumbar and abdominal pains and showed marked tenderness over all the pyelic and ureteral points on the left side. His condition grew progressively worse, and he died on the forty-second day. During the whole of the latter phase of the disease, the temperature was normal. Postmortem examination revealed an advanced pyonephrosis on the left side, and hypostatic broncho-pneumonia in the lower lobe of the right lung. (7) Respiratory Complications.--I have collected no evidence that the respiratory conditions so p r o m i n e n t both in the clinical and anatomical picture of the disease, may be imputable to its specific agent. It appears more probable that, as in most other infectious diseases, the lung condition is s e c o n d a r y - - d u e to the organisms of the respiratory tract, favoured by the conditions of diminished general and local resistance. T h e respiratory complications may take the u p p e r hand in the clinical picture, sometimes masking totally the real primary character of the disease. (8) Intestinal Helminthiases were c o m m o n with the following percentages : - Ascaris 25, ankylostome 46, trichuris 14, and strongyloides 10.

II. CLINICAL FORMS.

Paratyphoid C., as seen in British Guiana, presents then a varied s y m p t o m atology.

Our cases can be classified in the following clinical forms : - -

246

PARATYPHOID C. IN BRITISH GUIANA.

(1) Abortive and Plain Febrile Forms, of short duration, lasting from two to ten days, remittent or intermittent in type. (2) Protracted Forms, with remittent or intermittent pyrexia, without apparent localisation, are the most characteristic : to them belong the cases I had noted and grouped under the provisional diagnosis of " intestinal fever " since 1923. The course of these cases is usually benign. (Chart No. 2.) In uncomplicated cases a fatal termination is rare : in rare instances without appearance of definite localisation, the condition may gradually and progressively decline. The fever may persist or fall to normal during the latter stages. In some instances death may be due to the suppurative complications described. (3) Algid Forms.--The fever is high with deep remissions to normal or subnormal. The fall of the temperature is accompanied by profuse cold sweats ; the hands and feet are clammy and icy cold, the patient is pulseless, anxious, restless, and delirious; death occurs in collapse. A progressive ladder-like fall may be noted in these cases, death occurring in apyrexia (Chart No. 5). (4) Pulmonary Forms with prevalent involvment of the bronchi and lungs ; the physical chest symptoms are those of a plain bronchitis, lobar pneumonia or broncho-pneumonia. Nervous symptoms are usually marked with delirium and restlessness. The temperature is of a deeply remitting type. In one instance it remained persistently high. III.

DIFFERENTIAL DIAGNOSIS.

In the abortive and slight forms, as also in the protracted cases with a daily intermittent temperature, malaria fever is the first disease to be considered. Double infection, as we have seen, is very common ; a temperature resisting active quinine treatment, particularly if malaria parasites have been present in the blood, requires further investigation. In the protracted forms of long duration, septic fever due to deep-seated suppuration and tuberculosis must be considered. With typhoid fever, the clinical diagnosis is mainly based on the deeply remitting or intermitting character of the temperature, on the absence of intestinal symptoms, and of the intestinal complications so frequent in real enteric (h~emorrhage, perforation, tympanites). From the other parenteric fevers the diagnosis, on purely clinical grounds, appears much" more difficult and uncertain, but no cases of paratyphosus A or B have come under my observation in British Guiana. In the algid cases, the clinical diagnosis from an algid form of pernicious malaria is practically impossible, and, owing to the urgency of the symptoms, I have always administered quinine by injection as early as possible. The diagnosis of pneumonic or broncho-pneumonic forms was obtained exclusively by cultures from the blood or from the spleen after death. In the

GEORGE GIGLIOLI.

~47

bronchitic forms, the serious state of the patient, with delirium and high remittent temperature , is in contrast to the relatively slight lung lesions. Under this heading I again wish to emphasise and insist on the following important points : - (a) The absolute necessity of routine haemoculture for the investigation of protracted quinine-resistent fevers of obscure nature. (b) The importance of repeating the Widal test, with T.A.B.C., and eventually other emulsions of the sahnonella group of organisms at weekly intervals, and if necessary during convalescence. (c) The greater sensitiveness of the Widal and agglutination tests and their more marked specificity (exclusion of group agglutination) by the vital or cultural method. IV. PROGNOSIS. This is invariably good in the abortive and plain febrile forms. It is usually good in the protracted cases, but the possibility of renal or hepatic complications should be entertained. It is favourable in cases with slight bronchial involvement ; grave in the pneumonic and broncho-pneumonic forms ; unfavourable in algid forms. V. M O R T A L I T Y . Of ninety-two cases of confirmed paratyphoid C., thirty-two died. The case mortality was therefore 38 per cent. During the period October, 1926, to June, 1928, paratyphoid C. accounted for 33 per cent. of deaths from all diseases registered in Mackenzie Hospital. Though these figures give an accurate idea of the mortality as seen in hospital practice, they certainly do not correspond to the actual local mortality rate of the disease. The great mass of abortive, slight and mild protracted cases, undoubtedly pass unobserved, as they never apply for treatment, or are seen only as out-patients, and not correctly diagnosed. Such cases can only be recognised by being kept under careful observation, and by laboratory methods. Such mild cases as were detected all occurred amongst employees of the Company, who are obliged to report to the medical officers when ill. The actual mortality should be considerably lower than our hospital statistics show. The association of the disease with malaria infection, which was evident in 29 per cent. of our cases, must also be considered as an aggravating condition. During the period November, 1926, to August, 1927, the disease not only appeared in epidemic form m the district, but showed a very marked increase in its virulence. There were registered eighty-two cases, with thirty-two deaths (39 per cent.) ; of thirty-five cases which were admitted m our hospital during the period January, 1923, to October, 1926, no fatality was recorded. From

9.A~8

PARATYPHOID C. IN BRITISH GUIANA.

August, 1927, to June, 1928, the epidemic having subsided, the virulence of the disease equally decreased. Of twelve cases admitted only two (16.6 per cent.) died. VI.

EPIDEMIOLOGY.

In what follows it should be noted that for all cases observed prior to September, 1926, the diagnosis of paratyphoid C. is only clinical, and refers exclusively to cases of the prolonged daily remitting pyrexia type. For all cases recorded since September, 1926, the diagnosis has been bacteriologically confirmed. RACE, AGE AND SEX D I S T R I B U T I O N .

Table No. 1 classifies ninety-two confirmed cases of the disease according to race, age and sex. T h e y are in fair proportion to tl:e various elements of the local population. TABLE I.

Age.

Males.

Females.

Below 1 year .. A g e s 1 to 5 y e a r s

4 2 3 32 13 7

3 5 13 8 1

61

31

,, 6 ,, 15 ,, 16 , , 2 5 ,, 26 ,, 35 ,, 36 ,, 60 Total

,, ,,

,, ,, ..

I

Total.

1

J

Race Distribution.

5 5 8 45 21 8

Negroes , 57 East Indians 4 Aboriginal Indians 6 Portuguese 1 Mixed Races 24

92

92

GENERAL SANITARY CHARACTERISTICS OF THE DEMERARA RIVER DISTRICT.

The general sanitary conditions of the isolated dwellings along the Demarara River are of the worst. T h e y are surrounded by swamps and high bush ; in the rare instances in which latrines are to be found they are represented by simple, shallow holes, and teem with fly larvae. The sanitary conditions of the village of Christianburg are bad. The villages of Mackenzie, Akyma and Wismar are under control of the Demerara Bauxite Co., Ltd., and m u c h money and work have been, and are being spent, for their sanitary improvement and upkeep. Unfortunately there is continual contact between our population and that of the more insanitary section of the village of Christianburg, where quite a large number of the Company's labourers are living. FOOD POISONING.

This is currently associated with salmonella infections, and can be easily excluded in the etiology of the disease we are studying.

GEORGE GIGLIOLI.

~49

Organisms of the suipestifer-Hirschfeld type have only in very rare instances been associated with food poisoning. Hirschfeld strains of the eastern sub-type, as ours appear to be, are exclusively known as agents of paratyphoid fever in man. Apart from this, the following points are worthy of note :-(a) During the past five and a half years of observation, cases of the disease have occurred frequently, though in variable numbers. During the years 1923 and 1924, only sporadic cases were noted. During 1925 cases were more numerous, and grouped as to locality of origin. No fatal case was registered up to the latter part of 1926. From November, 1926, to April, 1927, the disease appeared in a severe epidemic form, with an exalted virulence, causing a high mortality. During the remaining months of 1927 to June, 1928, the disease has been frequently observed, usually in a mild form. (See Table No. 2 and Diagram.) (b) Foodstuffs which, if infected, are known to be the means of spread of salmonella infections, are very little used by the riverine population. Fresh beef and pork are sold only at Christianburg, and in limited amount, not exceeding the needs of the immediate neighbourhood. Cases of paratyphoid C., on the other hand, occurred throughout the whole river district, which comes under our observation (seventy miles approximately). (c) Cases occurred among East Indians, who did not use meat in their diet. (d) Five cases occurred in breast-fed infants, below one year of age. (e) In any given locality where the disease occurred, cases followed each other at intervals varying from a few days to several weeks. For instance :--In the small locality of " Old England," the first case registered, occurred in a child of eight months on the 22nd January, 1927 ; this case presented a suppurated arthritis of the shoulder (see above, Case No. 36), and had evidently been ill for a considerable time. Sixteen days later two more cases occurred in the same locality, also in children of nine and eleven months respectively. The next and last case occurred on the 3rd March, the patient being the mother of the first case recorded. For the mining Camp at Akyma, with a population of approximately 350, eighteen cases were registered from December, 1926, to June, 1928, at the following intervals : 11, 11, 3, 27, 10, 7, 7, 18, 2, 9, 18, 10, 83, 27, 150, 97, 20 days. It is improbable that any case escaped detection. Similar findings are given by the investigation of cases occurring in the numerous localities from which the disease was registered. The more or less noticeable interval separating the occurrence of cases points to successive infection, followed by the necessary period of incubation. Canoes, boats and timber punts provided for the widespread and rapid distribution of the infection throughout the river.

9,50

P A R A T Y P H O I D C. I N BRITISH GUIANA.

RELATION TO METEOROLOGICALCONDITIONS AND SEASONAL INCIDENCE. Table n shows no particular relationship between the rainfall and average mean temperature as registered at Mackenzie, and the number of cases of paratyphoid C. observed month by month from 1923 to June, 1928,with the exception of a marked decline in the incidence of the disease during the first half of the drought years 1924 and 1926. Cases occur more or less all the year round, but there is a decided increase during the winter months from November to May. June and July show the lowest incidence. MODE OF SPREAD OF INFECTION. No evidence was collected to incriminate the water supply. Milk is very scarce in the district; infection of food has been excluded above. Flies, never very abundant, were decidedly scarce at the height of the epidemic. Carriers, in form of abortive cases, slight ambulatory infections simulating malaria fever, and convalescent cases, are the most likely means of distribution of the infection, by more or less direct contact. We have seen how constantly and persistently B. paratyphosus C. was found in the urine of patients. I believe that urine is the most dangerous means of spread of the disease, not only on account of the large number of bacilli it harbours, but also in relation to the very insanitary habits of the population in this respect. The general state of sewage disposal in the district has been mentioned. Though some precaution is usually taken for the disposal of night soil, none whatever is taken as regards urine. Particularly during the night, urine is voided from the back steps of the houses, or anywhere in their immediate vicinity. Frequently on the same steps the meals are prepared, and the small children play and roll about on the polluted ground. During the rainy months the soil around the houses is moist and muddy, and the sun's rays weak ; the survival of virulent organisms is thus favoured. A small outbreak of five cases of paratyphoid C. in a very insanitary section of the village of Christianburg in May, 1928, gave a clear illustration of the importance of contact in the spread of the disease versus water pollution. The village had been flooded for some time, as the effect of heavy rains and spring tides. The creek which flows through it, and is the main source of the drinking water, was in direct connection with a large number of flooded pit latrines. The drain waters from the roads and the house yards flowed into this same creek, and in it as usual the children bathed and the women washed clothes. The high degree of f~ecal'pollution of this water was demonstrated at the time by a widespread outbreak of diarrhoea, with numerous cases of bacillary dysentery. The five cases of paratyphoid C. recorded, all occurred in a small block of houses, situated in a radius of about 50 yards at the following intervals :--seventeen, eleven, two and five days from 10th April, 1928. In spite of ample pollution of the creek from this particular block, no other case of paratyphoid C. was found in the rest of the village.

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PARATYPHOID C. IN BRITISH GUIANA. EPIDEMIOLOGICAL RELATION OF PARATYPHOID C. TO MALARIA FEVER.

Though the period of observation is short, and it is certainly premature to draw any definite conclusions, there appears to be a marked relation between the incidence of paratyphoid C. and malaria. This can be summarised as follows (see D i a g r a m ) : - (1) T o a low malaria rate corresponds a low paratyphoid C. rate. (2) The important outbreaks of malaria of 1924 and 1926 were accompanied and followed by a marked outbreak of paratyphoid C. (3) Paratyphoid C. continued to prevail during the months following the malaria epidemics of 1924 and 1926, when relapses and chronic infections were very numerous (1925 and 1927). (4) No fatal case of paratyphoid C. was noted, during the years 1923, 1924, 1925 and the first ten months of 1926, when malaria was relatively mild. (5) The virulence of paratyphoid C. infection was greatly increased during and following the 1926 malaria epidemic. The disease was prevalent and its case mortality exceptionally high. (6) With the decline in the malaria incidence, there has been a parallel decline in the incidence of paratyphoid C., with a marked fall in the case mortality. I~Z$,

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Diagram showing the relative incidence of malaria fever, paratyphoid C. and deaths from paratyphoid C. as observed in Mackenzie Hospital during the six-year period~ 1923 to 1928. (Continuous line, malaria cases ; black columns, paratyphoid C. cases ; black and white columns paratyphoid C. deaths.)

All my observations have been strictly limited to the Demerara River District. M y work has kept me from searching for the disease in other parts of the Colony. It is difficult to conceive the disease we have been studying

GEORGE GIGLIOLI.

258

as limited to the Demerara River, as conditions are identical in all the other riverine inland districts. KENNARD has reported on continued fever amongst sugar plantation coolies. Most medical men in the colony are familiar with cases of prolonged daily remittent or intermittent, quinine-resistant pyrexias, which give a negative T.A.B. Widal reaction. Recently, I carried out a Widal test (by the cultural method) on the serum of a medical man residing in Georgetown, who had suffered from a similar disease six months previously. I obtained very definite agglutination for B. paratyphosus C. in a dilution of 1 : 100. From what we have said of the relative incidence of paratyphoid C. and of malaria fever, it appears likely that the distribution of the two diseases throughout the Colony will be found to coincide. In other words, paratyphoid C. is mainly a rural disease, with highest incidence in the highly malarial districts of the Colony, such as the Canje, Berbice, Demerara, Moruca and Pomeroon River areas. VII. TREATMENT. DIET.

The diet need not be as strict as in enteric and other parenteric fevers, as the intestinal tract ~s not specially involved. During convalescence the patients can soon be put on a varied and nutritious diet. GENERAL TREATMENT.

General treatment is symptomatic, and carried out on the same general lines as for enteric. FIXATION ABSCESSES.

The formation of abscesses giving a pure culture of B. paratyphosus C., at the site of intramuscular quinine injections, has been mentioned as a frequent complication of the disease. The first cases were accidental, and developed in cases showing a double paratyphoid-malaria infection, which had received quinine injections for the treatment of the latter condition. With the first appearance of signs of localisation of the infection at the site of injection, it was noticed that the general symptoms invariably cleared up and convalescence began, often in spite of extensive suppurative lesions between the glutea] muscles. In some cases the transformation of the disease from a virulent septica~mia to a mild and localised suppurative condition was very striking. On the strength of these observations, it was considered justifiable to try to induce a fixation abscess by intramuscular injection of quinine, even in the absence of a malarial complication, in cases in which the disease appeared in a dangerous form. By administering quinine by intramuscular injection, we do not provoke

~4

PARATYPHOID C. IN BRITISH GUIANA.

the formation of a chemical abscess as is often the case with the injection of turpentine ; we simply cause a slight, and in itself in no way harmful, irritation of the tissues, which may determine the localisation of the infection, if the complex conditions of individual resistance of the patient, and of virulence of the infection, are such as to favour such an issue. In the case of hypervirulent infections the disease evolves rapidly to its fatal termination, however great the local tissue irritation we may produce ; on the other hand, in mild cases the organic defensive resources will be sufficient to resist not only the general infection, but also the localisation of the infection in tissues only mildly irritated, as in the case of quinine injection. In conclusion, I believe that as a provocative of fixation abscesses, in paratyphoid C. at any rate, quinine by intramuscular injection, through the mildness of the irritation it determines, has the advantage of limiting its action to those cases which are most apt to be benefited by abscess fixation. The interesting clinical characteristics of these abscesses, their extremely mild s?mptomatology, and their immediate response to simple surgical treatment, have already been discussed. Out of fifty-nine severe cases (complicated or not with malaria fever) which received one or more intramuscular quinine injections, fifteen (25.4 per cent.) died within the first five days after admission ; nine (15.2 per cent.) died after longer periods, without developing symptoms at the site of injection ; fifteen (25.4 per cent.) recovered without local complications ; and twenty (34 per cent.) developed fixation abscesses at the site of injection. Of the latter eighteen recovered and two died. Of these, one died on the twenty-fourth day of the disease with bilateral pyelonephritis, and the other on the forty-second day with extensive sacral sores and left pyonephrosis. In both these cases the septica~mic phase of the disease had been overcome ; death followed the onset of secondary complications. Amongst cases in which an abscess was produced, the mortality was only 10 per cent. (from secondary complications) against a general case mortality of 37 per cent. The indication for the induction of a fixation abscess appears most marked in the severe purely septie~emic cases with marked delirium and high temper~itures ; in these, tile disease is usually and rapidly cut short in the week following the injection. There is little chance of success in the cases of severe pneumonie or algid forms, in which the rapid evolution of the disease will rarely allow time for the formation of an abscess. In such cases the use of turpentine as a provocative agent might be more appropriate. From what,precedes, it appears evident that in presence of slight paratyphoid infections, with malaria as a complication, quinine should be administered per os and not by injection, in order to avoid the risk of determining an abscess, which, in a mild form of the disease, would be a totally unnecessary and annoying complication.

GEORGE GIGLIOLI.

255

VIII. PREVENTION. The following are the prophylactic precautions which were taken in order to limit its spread and to prevent its future occurrence amongst the employees of our Cempany. VACCINATION. TONBRAECK, in 1918, found that rabbits immunised against B. paratyphosus B. showed no immunity to B. suipestifer. SCHUTZE, in 1922, by immunising rabbits against B.paratyphosus B. failed to protect them against B. suipestifer. On the contrary, complete immunity against the latter was obtained if the animals were vaccinated with B. aertrycke or Hirschfeld strains. PERRY and TIDY, in 1919, in an outbreak of food poisoning caused by Salmonella Newport, studied the effect of typhoid-paratyphoid inoculation. They concluded that typhoid-paratyphoid vaccine (T.A.B.) does not protect against infection with B. aertrycke (Newport). SAVAGE and BRUCE-WroTE have investigated the subject of cross-immunity among different types of the Salmonella group as demonstrated by animal experiments. These authors noted that cross-immunity for B. aertrycke and B. enteritidis is complete and reciprocal. A similar relation appears to exist between B. paratyphosus B. and B. aertrycke. B. aertrycke was found to produce partial immunity against B. suipestifer, while B. paratyphosus B. failed to do so. Two of our cases had received previously one dose of T.A.B. vaccine prepared by the Government Bacteriological Laboratory. A ward maid, who evidently contracted the disease in hospital, had had a complete vaccination (three doses) ~ith Parke Davis & Co.~s typhoid-paratyphoid vaccine. Her blood was rich in T.A.B. agglutinins, yet she contracted the disease in a very severe form. It appears unlikely, therefore, that the current trivalent vaccines have any preventive action against paratyphoid C. CASTELLANI,during the war, prepared a tetravalent T.A.B.C. vaccine for the use of the Serbian army, using strains of paratyphoid C. isolated by HIRSCHFELD. I have prepared a similar tetravalent vaccine cemposed as follows : - -

B. B. B. B.

typhosus paratyphosus paratyphosus paratyphosus

. . . . . . A . . . B . . . C . . .

. . . . . . . . . . .

500 million ~ 250 ,, ~ To 1 c.cm. 250 ,, [ ) 500 ,,

For B. typhosus and B. paratyphosus C., five locally isolated strains are being used ; for paratyphoid A and B, strains obtained from the N.C. of type-cultures are being employed at present, as these organisms have never been isolated in our laboratory. The emulsions are killed by heat (two hours in the water bath

256

P A R A T Y P H O I D C. 1N BRITISH

GUIANA.

at 60 ° C.), and preserved in 1 per cent. lysol. The vaccine is administered in three doses, at seven days' interval, of ~, 1 and 1 c.cm. respectively. Local and general reactions are always very mild, more marked at the second dose ; usually absent at the third. Over 500 persons have already received a complete course of injections. It is hoped to carry this number to approximately 1,000 in the next few months. GENERAL

MEASURES.

Isolation, disinfection of houses and their immediate surroundings, bedding, clothing and latrines was carried out as usual. In labour camps, in order to prevent the spreading of the infection by urine, special galvanised urine buckets were placed at night by the doors of each bunkhouse, and removed and disinfected in the morning.