THE ENTERIC FEVERS (Typhoid and Paratyphoid Fevers)

The annual occurrence in Britain of one or more outbreaks of enteric fever and the recent one in Aberdeen indicates that, in spite of sanitary precautions,
the risk of contamination of water and food supplies with the enteric group of organisms still persists. S. typhi and S. paratyphi B, the organisms commonly met with in the British Isles, are excreted in the stools and urine during the course of the illness. The unsuspected ambulant case, the missed case, the temporary carrier and the chronic carrier play a very important part in the dissemination of enteric fever. It is probable that even with efficient chemo­therapy from 2 to 5 per cent. of all cases of typhoid fever become permanent carriers. That the incidence of the chronic carrier state is higher in women than in men is unfortunate when we consider the possibilities of contami­nation of food in course of preparation. Although the fascal carrier is more commonly encountered, the urinary carrier is potentially more dangerous. The organisms are discharged intermittently in both stools and urine, so that repeated bacteriological examinations are essential before the carrier state can be excluded.
Although isolation of the pathogen from fascal and urinary specimens is the only exact method of diagnosing carriers, preliminary examination of the blood serum may serve as a useful " screening " test for carriers of S. typhi when large numbers of suspects have to be reviewed. Antibodies for the Vi antigen are almost always to be found in fairly high titre in carriers ; so that if a preliminary blood test is carried out, attention can be directed particularly to those with such antibodies.
Outbreaks, then, are usually a result of the contamination of food or water by a missed case or carrier. Milk or milk products, prepared meats, uncooked vegetables, fruit and shellfish constitute the usual vehicles of infection. A nurse may contract the disease in the course of her duties ; this usually indicates carelessness in the washing of hands. It is important to make a specific pro­hibition of the eating of any food by the attendant in the ward or room w^ere the disease is being nursed.
Typhoid and paratyphoid fevers are notifiable diseases. The incubation period of typhoid infections is from 12 to 14 days, and of paratyphoid B from 10 to 12 days.
Prevention and Epidemiological Control.—The control of typhoid fever is essentially a problem for the local Public Health Authority and embraces such factors as an efficient system of sewage disposal, a safe water and milk supply, the detection of carriers, the supervision of shellfish, the control of the house-fly and effective supervision of premises where food is sold or prepared.Careful supervision of sewage and water is a commonplace in the large towns, so that widespread epidemics of typhoid are now unusual. In country districts, however, defective cesspools, flooding or ineffective disposal of sewage are still commonly the source of localized outbreaks. Articles of food, especially cold meats and tinned ham and beef have now replaced water as the vehicle of infection, especially of paratyphoid fever, and here the towns are in as much danger as the countryside. Although day-to-day control by Public Health Departments forms an important part of the protection of the public, the early diagnosis of the infected case by the practitioner is of prime importance both in stemming an incipient epidemic and in stopping it once it has started. The value of early blood culture in cases of continued fever must here be emphasized; and the golden rule is to carry out a blood culture on any case which has an unexplained pyrexia for more than three days. A specimen of blood for agglutination tests should be submitted at the same time. The impression that it is only worth while to examine for agglutinins after the end of the first week of illness is quite erroneous. An early specimen may show their presence in low titre, and if a further examination in three or four days shows a rise in titre the diagnosis is almost certain. Of course, previous inoculation against typhoid or paratyphoid to a large extent invalidates the Widal test and no reliance can be placed on the results of a single examination in such persons.
The subdivision of the typhoid group by specific bacteriophages into a number of " phage " types has been of great assistance in tracing the exact source of the epidemic. This has led to greater precision in attributing cases to a particular carrier. Typing may also be of value in indicating the place from which infection has come. In this respect it should be appreciated that the popularity of holidays abroad often introduces a type of organism not indigenous to the country in which the patient takes ill.
Where a number of cases occurs in a district, the practitioner will usually be informed by the local Medical Officer of Health, and co-operation with him in attempts to investigate the source of the epidemic will be of the greatest benefit. The practitioner is in a favourable situation for seeing formes frustes examples of infection and he should bear in mind the fact that many of the illnesses, especially of paratyphoid fever, are mild; diarrhoea may never occur and many cases masquerade as influenza, tonsillitis or bronchitis. In his daily practice, too, he should insist on the boiling of water and milk and in the avoidance of all foods eaten in a raw or partially cooked state. A campaign against flies should be instituted, and here the use of gammexane sprays and dicophane (DDT) play an important part.
Immunisation.—TAB vaccine (either phenolized or acetone-treated) usually contains in each ml. 1,000 millions of S. typhi and 500 millions each of S. paratyphi A and B. Cholera is often included in the vaccine (TABC) and this is a convenient way to immunise persons travelling to the East. The initial dose in adults is 0-5 ml. followed seven to ten days later by i ml.; to children between three and ten years of age 0-25 and 0-5 ml. may be administered. A third injection of i ml. (adult) or 0-5 ml. (child) should be given one week later to persons who are going to live in an endemic area. The injection is given subcutaneously, and as systemic disturbance is liable to follow, any strenuous exertion should be avoided for 24 hours after each dose. Pulmonary tubercu­losis, diabetes mellitus and chronic kidney or vascular disease are usually listed as contraindications to inoculation, but when the person is to reside in an endemic area the risks of inoculation are less than the danger of acquiring the disease. The vaccine should not be administered during late pregnancy or during the course of an acute infection. The administration of a more potent vaccine intradermally (0-2 ml.) has been claimed to result in fewer side-effects. Comparative trials have not been reported.
Protection is attained within two weeks of the final injection, and after lasting for some months gradually lessens over a variable period. When a person has to live permanently in an endemic area an occasional booster injection of 0-5 ml. should be given.
Curative Treatment.—Chemotherapy.—Chloramphenicol may now be regarded as a specific form of therapy and should be given to every patient. For the best results early administration is desirable, although success may still be attained when the patient has already been ill for one to two weeks. The dose recommended is i to 2 g. daily for a period of 15 days—the long period being desirable to reduce the tendency to relapse. A high initial dose is unwise, since a " Herxheimer " effect has been noted in some severely ill patients. Treatment with chloramphenicol often produces remarkable improvement within 24 to 48 hours, especially when begun early, but it should be remembered when treat­ment is started late that in spite of the patient's well-being the ulceration of the bowel and muscular degeneration resulting from toxasmia are still present. It is, therefore, essential to maintain complete bed rest for a period of two to three weeks, until healing of the ulcerated bowel has occurred. Relapse is still a prominent feature of the disease, but fortunately responds to a second course of chloramphenicol. Ampicillin is not recommended for the treatment of the acute infection.
General Management.—The patient must be kept strictly recumbent, but his position should be altered several times daily. Mental rest is essential, and visitors must be excluded. A four-hourly chart must be kept and arrangements made for the prompt notification of serious symptoms to the physician. Stools, urine and other discharges, wash water, soiled linen, nursing utensils, etc., require to be carefully disinfected, and the patient's crockery, cutlery, etc., must be boiled after use. Measures should be taken to rid the sickroom of flies. The nurse must on no account prepare or handle food which is to be consumed by other members of the household.
The mouth and skin require regular and careful cleansing, and precautions have to be taken to prevent the development of pressure sores.
Retention of urine is liable to occur and should receive appropriate treat­ment. Inspection of the stools, abdomen, lung bases and heart should form part of the physician's daily routine examination.
Diet.—Although treatment with chloramphenicol will often produce rapid amelioration, it must be emphasized that, if bowel ulceration has occurred, time for healing must be allowed. The duration of a strict dietetic regime is now greatly shortened ; but it is essential in the early days of treatment to enforce a low residue diet and to be sure that all evidence of intestinal inflammation has subsided before relaxing these precautions. During the early days of the illness a fluid diet should be administered. The use of a " composite " food such as Complan (Glaxo)—even if only for a part of the diet—makes it easy to ensure that the intake is adequate. Towards the end of the first week, in addition to 2 pints of milk daily, such readily digestible articles as lightly boiled eggs, custard, ice-cream, junket, cream cheese, milk shapes, milk puddings, jellies, mashed potatoes with butter or gravy, prepared breakfast foods, stewed apples, plain chocolate, thin bread and butter, sponge cake, and minced chicken or beef may be included in the diet.
Complications.—As soon as the patient has been effectively brought under chemotherapeutic control, the symptoms and signs which were formerly dreaded—persistent diarrhcea, meteorism and intense toxaemia—either fail to appear or rapidly disappear. Only two points need to be borne in mind; first, ulceration may still be extensive even when the patient seems well so that perforation or hsemorrhage still occasionally occur; second, despite clinical improvement, organisms may persist in the stool so that the patient should not be assumed to be free from infection. Relapse, as has already been indicated, is a common occurrence and may even occur after the 15-day course of treatment.Haemorrhage and Perforation —The practitioner must be on the lookout for these serious complications, especially during the third week of the illness. On the first appearance of blood in the stools or a sudden drop in temperature accompanied by a rising pulse rate, 15 mg. of morphine and 0-6 mg. of atropine sulphate should be injected without delay. Further treatment will depend on the severity or persistence of the hsemorrhage but preparations should be made for blood transfusion.
Surgical assistance must be summoned immediately perforation is suspected. Morphine should be withheld until the diagnosis is confirmed.
Phlebitis.—Thrombosis in the veins of the lower limbs is a common com­plication during convalescence. The affected limb is immobilized with pillows for two weeks, after which period gentle massage and passive movements may be started. Suitable analgesics will help to relieve the early pain. The use of anticoagulants is contraindicated because of the danger of precipitating haemor­rhage from the bowel.
Other Complications.—The pain of cholecystitis can be relieved by the local application of hot fomentations and the hypodermic injection of pethidine or morphine and atropine.
Periosteitis or osteomyelitis must be treated on surgical lines. Material from a periosteal abscess may contain typhoid bacilli, and soiled dressings should be handled with care.
Convalescence.—It is advisable to confine the patient to bed for at least 14 days after the temperature has returned to normal. By this time the danger of relapse is usually past. Six consecutive negative cultures for enteric organisms must be obtained at two- or three-day intervals from stools and urine prior to the release of the patient from isolation. The rapid clinical recovery can en­courage the clinician to think that bacteriological clearance is also rapidly achieved. This is not the case; chloramphenicol is not bactericidal and persistent excretion of organisms is common during convalescence. If the patient is involved in the preparation of food, specimens of fasces and urine should be examined six weeks after discharge from hospital and the Public Health Department should maintain an interest in the patient for a year.
Treatment of Carriers.—As was emphasized in the discussion of diph­theria carriers, the carrier state often superimposes itself upon some pre­existing chronic condition and this makes the treatment of the established carrier far from satisfactory. Unfortunately many chronic carriers are unaware that they ever suffered from the disease. In the case of a urinary carrier, a full examination of the urinary tract is desirable, for it is sometimes possible to rectify a coexistent abnormality. The faecal carrier state is often associated with chronic cholecystitis and, perhaps for this reason, is commoner in women;modern methods of anaesthesia have so greatly reduced the hazards of surgical interference that cholecystectomy should receive serious consideration in such cases. When the carrier state is found to arise from a chronic bone lesion, appropriate surgical measures are usually successful.
There is still no method which can be guaranteed to eradicate organisms from the chronic carrier. Assessment of cure is made difficult by the fact that excretion of organisms is usually intermittent and, even without treatment, negative results may be obtained over a period of a few months. For this reason at least twelve months of freedom from excretion are essential before a carrier is regarded as cured. Recently, impressive results have been obtained by the oral administration of ampicillin, ro g. six hourly, along with probenecid, ro g. twice a day. The treatment must be continuous and persistent over a period of three months. Short term treatment is valueless. The development of erythe-matous rashes during the preliminary stages of treatment is sometimes seen but may be ignored. The only satisfactory test of cure is the examination of faecal specimens for pathogens and this should continue until negative results have been consistently obtained for one year.
It is impractical to expect the chronic carrier to remain in hospital during this long period of treatment and bacteriological follow-up. He (or more frequently she) may be allowed home under the supervision of the family doctor and the Medical Officer of Health who will be responsible for obtaining further fascal specimens for bacteriological examination. Before dismissal from hospital, the members of the household should be immunized with TAB vaccine.
Finally, it should be emphasized that in Britain, where endogenous enteric is now uncommon, the most rigorous steps should be taken to eliminate the carrier state after an acute attack. A device which has great value in monitoring individual households or the community as a whole is the " sewer-swab ". These can be inserted into the domestic sewer pipe or main sewers and after remaining there for a period of days are submitted to special bacteriological examination. They often disclose unsuspected pathogens.