The different classical forms are seen with their usual characteristics. Campani and Gallotti reported that in a series of cases of typhoid and paratyphoid fevers occurring in 144 nonvaccinated civilians and 341 vaccinated soldiers on the Italian front the case mortality rate from typhoid fever in the vaccinated patients was 8.6 per cent and in the paratyphoid A and B cases 4.6 and 7.8 per cent, respectively. Among the unvaccinated the case death rate for typhoid was 20 per cent and for the paratyphoid cases nil. They found that in both groups about 42 per cent of the patients had a febrile period lasting into the fourth week and that the average duration of fever was, among the soldiers, 24.5 days and among civilians 28 days. They state that the febrile curve instead of being irregular and low in the vaccinated, was high and decidedly more regular than among the nonvaccinated. Splenomegaly and nervous phenomena were more frequent among the vaccinated. These workers concluded that vaccination had lessened both the mortality and the severity of the disease.

Freund 48 reported typhoid infection in the German Army and concludes that among the vaccinated cases there were more remissions and intermissions as well as a great number of mild cases. The fever was milder but the total duration of the disease was not shortened. No change in the frequency of the complications or relapses resulted on vaccination, and mortality given among the vaccinated was 8.3 per cent.

Hawn, Hopkins, and Meader,14 in describing the 38 cases studied in an outbreak among American troops in England, found clinical symptoms similar to the cases described by Vaughan. The initial chill occurred in 16 per cent, diarrhea in 58 per cent, constipation in 21 per cent, abdominal pain in 6 per cent, and epistaxis in 2.6 per cent. Rose spots were described in 19 cases, splenomegaly in 9 per cent. Blood cultures were positive in 12 cases and the mortality was 13.15 per cent.

There was a somewhat progressive increase in severity with lapse of time after inoculation in individuals to whom vaccine had been administered from one to six months before the patient was taken sick (11.6 per cent severity). When from 13 to 18 months had elapsed, 15.9 per cent were classified as severe. It appeared that the average severity of the disease was fairly constant throughout the first eight months following inoculation, after which it gradually increased. The proportion with relapse did not appreciably differ.

COMPLICATIONS, SEQUELÆ, AND CONCURRENT DISEASES

The complications and sequelæ of typhoid fever during the war afforded nothing new from either a clinical or pathological point of view. Among the more important of these were 4 cases of general septicemia, with 4 deaths; 2 cases of acute endocarditis, with 2 deaths; and 7 cases of myocardial insufficiency, of which 2 resulted fatally. Important complications of the respiratory tract were 26 cases of bronchitis, with 6 deaths; 59 cases of bronchopneumonia, with 39 deaths; 29 cases of pneumonia, of which 24 terminated fatally; and 18 cases of pleurisy, with 6 deaths. Hemorrhage was recorded in 11 instances, with 8 deaths; and diarrhea as a complication in 5 cases, of which 3 terminated fatally. Enteritis and colitis occurred in 12 instances, with 2 deaths; and peritonitis in 8, with 7 deaths. There were 2 deaths among the 4 cases of acute

nephritis. Altogether 209 complications were deemed as being of sufficient importance to be reported, with 151 deaths.

Typhoid fever was reported as concurrent with other diseases in 368 instances. Of these, 60 terminated fatally, giving a case mortality of 16 per cent. The more important diseases with which it was concurrent are given in Table 8.

TABLE 8. Typhoid Fever. Concurrent with other diseases, enlisted men, United States Army, serving in the United States and Europe, April 1, 1917, to December 31, 1919

Nichols, who made a somewhat exhaustive study of the "carrier" state during the World War, classified carriers as "incubationary," "convalescent," and "contact." The percentage of cases that develop the carrier state of one class or another has been variously estimated as being from 9 to 50 per cent, women constituting the majority, three-fourths of the carriers being of the intestinal type.

The bacteriological examination of the stools and urine of food handlers at stated intervals, and examination of convalescents from typhoid for the carrier state prior to their discharge from hospital, was a matter of routine during the World War, and by means of this administrative procedure a few carriers were detected. According to Nichols, the results of examination of about 30,000 food handlers during the war demonstrated less than 0.1 per cent carriers among healthy males. Gay states that 7,500 carriers are being added to the civilian population in the United States each year. There were 64 recorded carriers among the primary admissions to hospital during the war. Instructions governing medical officers, A. E. F., in the determination of a carrier state were as follows: 50

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Typhoid and paratyphoid patients excrete the bacilli, frequently with their urine and practically always in their feces. This is most likely to occur during the third and fourth week of the disease, the condition may persist throughout convalescence and not infrequently longer. It is, therefore, important not to release the convalescent typhoid or paratyphoid fever patient until he ceases to excrete these bacilli.

Three negative cultures of the urine and feces at six-day intervals should be required before release of patient, the first not earlier than one week after temperature curve has become normal.

Some persons who have never had a clinical history of the disease may excrete typhoid or paratyphoid bacilli. It is important to detect such carriers in any occupation, but especially among cooks and handlers of foodstuffs. In such a carrier survey, two examinations should be done on each individual.

No definite lesions were found in incubationary and contact carriers. The liver and kidney showed lesions in convalescent carriers. In intestinal carriers with lesions in the gall-bladder, bile-ducts, or both, the organism was demonstrable in the stools. In urinary carriers the focus was found in the kidney, especially in the pelvis.

According to Nichols,49 carrier strains did not differ from others and could not be differentiated by cultural or other tests. In determining the carrier state serological examinations were suggestive, as more than 50 per cent gave positive agglutination tests. Such examinations, however, were of little value in the case of convalescents from the disease or in the recently vaccinated subject. The organism was found in the duodenal contents or feces in the intestinal type of carriers and in the urine in urinary carriers. It was the custom to require at least three consecutive examinations of the feces and urine of convalescents from typhoid before dismissing the possibility of an existing carrier state.

In the United States it was the policy to collect all chronic typhoid carriers in the Army at the Walter Reed General Hospital, Washington, D. C., for further observation and treatment.51 At the time the armistice went into effect arrangements also had been completed for the establishment of a special hospital in France, near Dijon, for the treatment and study of chronic "carriers" of all types in the American Expeditionary Forces.

An essential in the successful treatment of typhoid carriers was location of the focus of infection which, though usually single, sometimes was multiple. Where the focus was a single one, as for example, the gall-bladder, treatment by excision usually effected a cure. Where the foci were multiple, as for example in the gall-bladder and in the bile-ducts, removal of the gall-bladder did not result in a cure.

Nichols, Simmons, and Stimmel 52 reported on the surgical treatment of typhoid carriers at the Walter Reed General Hospital in 1919. Seven cases are included in this report; 6 were intestinal carriers and 1 urinary. Four of the former were cured by removing the infected gall-bladder, and the urinary carrier was cured by removal of the infected kidney. In two of the intestinal carriers failure was attributed to the gall-duct being infected as shown by cultures of the duodenal contents. Operation was not recommended for at least six months after recovery from the primary disease, as in many instances the carrier state was of temporary duration. Henes 53 reported favorably upon the surgical treatment of typhoid bacillus carriers at the United States Army General Hospital No. 12 during the war.

In spite of all known methods of treatment, some chronic carriers continued to excrete bacilli. The commanding officer of the Walter Reed General Hospital reported several such cases to the Surgeon General in April, 1919.54 These cases had been operated upon, but foci of infection remained. The procedure followed in such instances was to discharge the individual from the Army, at the same time notifying the State board of health having jurisdiction.55

DIAGNOSIS

For many years, particularly since prophylactic vaccination was made mandatory, the Medical Department of the Army has stressed the importance of the scientific and early diagnosis of typhoid fever. Before we entered the World War it was required that the diagnosis be based on isolation of the organism and that a culture of the isolated organism be sent to the Army Medical School at Washington for confirmation. This practice was continued during the World War except that organisms isolated in France were sent for confirmation to the central medical department laboratory at Dijon.

A prompt report of cases of enteric fevers was insisted upon by the chief surgeon, A. E. F.56 For purposes of classification a division was made into proven cases, clinical cases, suspects, convalescents, and healthy carriers. Diagnoses were reported by telegram to the chief surgeon, A. E. F. With the development in France of several foci of infection-December, 1918, and January, 1919-the chief surgeon, A. E. F., issued a special circular letter relating to the typhoid and paratyphoid fevers. The following notes on diagnosis were incorporated in this letter: 50

In individuals previously vaccinated against typhoid but who have completely lost their immunity, infection similar to that found in the unvaccinated occurs, giving rise to the symptom complex characteristic of typhoid fever.

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Infections occurring in the vaccinated individuals who still possess a certain degree of resistance to infection results in the appearance of atypical clinical pictures, such as abortive types of typhoid and paratyphoid in which the constitutional symptoms are mild but with slight febrile reaction of atypical type and few if any rose spots. The onset may be either insidious, with headache, loss of appetite, and fatigue, or acute and associated with chills, vomiting, intestinal cramps, and diarrhea. Fever may be wholly absent or evanescent in character and determined only if observations are made within the first 48 to 72 hours. A low type of temperature, with daily fluctuations of from 98.6° to 100.4°, suggestive of the presence of tuberculous disease, may persist for a week or 10 days. It is in this class of cases that blood cultures taken early in the course of the disease, and repeated if negative, frequently give definite information concerning the nature of the infection. Ambulatory types of typhoid are not uncommon and the first indication of the existence of the disease may be furnished by the occurrence of intestinal hemorrhage or perforation.

The vaccinated individual protected against general systemic infection may still act as a carrier of typhoid infection and frequently shows clinical manifestations of local disease of some portion of the gastrointestinal tract, while the characteristic symptom complex of typhoid fever due to general infection, namely, continued fever, rose spots, and enlarged spleen, may be wholly absent.

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Atypical modes of onset.-(a) Acute onset with symptoms simulating meningitis. Lumbar puncture differentiates. (b) Acute onset with intense, usually generalized bronchitis or symptoms suggestive of lobar or bronchopneumonia. (c) With chills, fever, vomiting, cramplike pain in abdomen, sometimes localized in right iliac fossa and suggesting appendicitis. (d) With symptoms of acute nephritis. Attack begins suddenly, with nausea, vomiting, pain in lumbar region, diminution in secretion of urine, which is highly colored and contains albumin and casts. (e) Special mention should be made of the ambulatory type of typhoid in which the symptoms are slight, consisting simply of headache and lassitude associated with mild gastrointestinal disturbances. The patient is at no time confined to his bed, and intestinal hemorrhage or perforation may furnish the first clue with regard to the existence of typhoid. (f) In the above atypical modes of onset early blood cultures are of importances in differentiation.

In the differential diagnosis influenza, acute miliary tuberculosis, sepsis, and malarial fevers must be differentiated. Local and unexplained gastrointestinal derangements, as

gastritis, diarrhea, dysentery, enteritis, appendicitis, and inflammation of the bile passages, occurring with or without fever should be regarded with suspicion when cases are admitted from commands in which cases of typhoid or paratyphoid fever have occurred.

Laboratory diagnosis of typhoid and paratyphoid fevers.—Bacteriological procedures are of great value (1) for the certain and early diagnosis of suspected cases; (2) to determine carrier state in convalescent positive cases; (3) to detect carriers in otherwise normal individuals.

Blood cultures offer the most certain method for early diagnosis of undetermined fevers, and it should be kept in mind that the earlier in the disease the blood culture is taken the more likely is the result to be positive; thus, in positive typhoid fever the chance of successful blood culture declines from 90 per cent during the first week to 40 per cent during the third week. In paratyphoid A fever, because of the frequently short and mild febrile period, the prompt and early blood culture is all the more necessary. Relapses are more common in paratyphoid than in typhoid, and taken at such a time, blood culture yields positive results in every case.

The following method of blood culture is recommended as being suitable in all cases of fever of undetermined etiology.

(a) When laboratory facilities are at hand, take 10 c. c. of blood from a vein at the elbow. Place 3 c. c. in each of two flasks containing 100 c. c. of plain broth. Place 1 c. c. in tube of agar (melted and cooled to 45° C.); immediately mix and pour plate. Place remainder of blood in dry sterile test tube to separate serum for such serological tests as may be suggested.

The two flasks and plate are incubated and examined the following day. Transplants are made to plain agar slants, or, better, Russell's double sugar agar. In cases of development of Gram-negative motile bacilli on agar slants, emulsions should be made and agglutination tests done with immune sera for final identification.

Frequency of nonagglutinability of recently isolated typhoid cultures should be kept in mind. Negative blood culture in suspected typhoid fever means little. Repeat if clinical conditions indicate.

(a) If the blood culture specimen can not be taken directly to the laboratory, filtered sterile ox bile is most useful, 5 c. c. in a tube. To such sterile ox bile 5 c. c. of blood is added, the tube closed with a sterile paraffin cork, carefully packed, and sent for examination to the nearest laboratory. Bile medium is furnished in chest No. 1, transportable laboratory, United States Army, expeditionary force model. Additional supply of this medium may be obtained as needed from central Medical Department laboratory, A. P. O. 721.

Bacteriological examination of feces is second only to blood culture as an important means of positive diagnosis. It is especially important in paratyphoid B fever.

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The Widal test-In view of previous vaccination with T. A. B., vaccine has been generally held of little or no value; however, it should be stated that the determination of agglutinin titer of patient's serum at intervals of one week and the demonstration of progressive and marked increase of agglutinin content of the blood offer, especially in the absence of positive blood culture, excellent evidence as to the etiology of the disease. Thus, in typhoid fever an agglutinin titer (Widal test) of 1 to 40 during the first week of the disease may advance to 1 to 1280 during convalescence. In paratyphoid B fever the titer frequently advances to 1 to 2,560; however, in paratyphoid A fever it may not reach 1 to 640. Formalinized and standardized bacterial suspensions of B. typhosus B, paratyphosus A and B, paratyphosus B may be obtained on request from the central Medical Department laboratory, A. P. O. 721.

In the series of cases studied by Vaughan,3 blood cultures were made from 274 cases and typhoid or paratyphoid bacilli were isolated in 180 cases, or 65.7 per cent. Of these 180 positive results, 143 were positive on the first culture, 25 on the second culture, 3 on the third, 9 on the fourth, and none on the fifth, showing the value of repeated culturing. In the case of the epidemic occurring in the Camp Cody replacement unit, 32 per cent of the blood cultures taken in England were positive and 88 per cent of those taken at Cherbourg; in the Prauthoy epidemic 16 per cent were positive; in the Curel epidemic 88 per cent; and in the Marseille epidemic 28 per cent were positive. This is a