S. A. Kamat, C. Herzog

Typhoid: Clinical Picture and Response to Chlorarnphenicol Prospective Study in Bombay (1972) Summary: The clinical picture of 78 cases with proven typhoid and 18 cases with proven paratyphoid A fever is presented. The diagnosis was made by isolating the organisms from the blood. The Widal test could not be used as a diagnostic criterion. By means of chemotherapy with chloramphenicol (initial dose 30-40 mg/kg body weight) defervescence was achieved within an average of 4.5 days. The course of the disease was generally mild; one patient with typhoid fever died. The average hospital stay was 19 days. Four patients of the typhoid fever group were readmitted with a relapse. The laboratory examinations included blood clot culture, phage typing, Widal test, haemoglobin, leucocyte count, transaminases, serum bilirubin, and routine examination and culture of stool and urine. Forty-two patiems were infected with intestinal parasites and 25 with Shigella organism. The findings are discussed and compared with findings of similar studies of enteric fever.

Introduction With the introduction of chloramphenicol in 1948 (36) the natural course of typhoid fever changed to become shorter and less severe. This therapeutically induced change was followed by further modifications of the clinical and epidemiological pattern during the last decades. These may be due to various other factors such as quality of nutrition, standard of hygiene, immunisation status of the population, extent of diangnostic procedures, or even changes of the pathogenic agent itself. Moreover, pathological manifestations may vary in different areas of the world, e.g. complications such as intestinal perforation and haemorrhage are less often described among patients in India, and mental disturbances seem to be common in Africans (4). A prospective clinical study of typhoid fever was undertaken in Bombay in order to analyse the clinical manifestations and complications, to study the response to chloramphenicol, and to establish comparisons with the clinical picture elsewhere (7).

Zusammenfassung: Typhus abdominalis: Klinisches Bild und Therapie mit Chloramphenieol. Prospektive Studie in Bombay (1972). Es wird fiber das klinische Bild yon 78 Fallen mit nachgewiesenem Typhus abdominalis und 18 Fglten mit nachgewiesenen Paratyphus A berichtet. Die Diagnose wurde dutch Isoliernng der Erreger aus dem Blut gestelIt. Der Widal-Test konnte nicht als diagnostisches Kriterium verwendet werden. Unter der Chemotherapie mit Chloramphenicol (Initialdosis yon 30-40 mg/kg KSrpergewicht) trat im Durchschnitt nach 4,5 Tagen Entfieberung ein. Der Krankheitsverlanf war ira allgemeinen leicht. Ein Patient mit Typhus abdominalis verstarb. Die durchschnittliche Hospitalisierungsdauer betrug 19 Tage. Vier der Patienten mit Typhus abdominalis wurden mit einem Rfickfail erneut hospitalisiert. Die Laboruntersuchangen umfagten Blut-(,clot') Kultur, Phagentypisierung Widal-Test, H~imoglobin, weiBes Blutbild, Transaminasen, Serumbilirubin, Stuhl- und Urinuntersuchung sowie StuhI- und Urinkultur. Eine Infektion mit Darmparasiten land sich bei 42 und mit Shigellen bei 25 Patienten. Die Befunde werden diskutiert nnd mit den Erfahrungen aus iihnlichen Studien fiber Typhus abdominalis und Paratyphus verglichen.

12 to 55 years, the majority of patients being between 18 and 30 years. In all patients admitted to the fever wards of the Kasturba Hospital a blood clot culture, Widal test (typhoid O- and H- and paratyphoid A H-agglutinin titer), leucocyte count andurine examination were performed routinely. In the proven enteric fever cases the following investigations were performed one and two weeks after the start of therapy: Widal test, total and differential leucocyte count, haemoglobin, transaminases, serum bilirubin, routine urine examinations, microscopic stool examination, stool and urine culture. A second blood clot culture was made prior to discharge. Phage typing was done on half the strains of Salmonella typhi and Salmonella paratyphi A isolated. After isolation of the organisms, specific therapy with chloramphenicol was started, usually on the third day after admission to hospital. The hospital stay lasted an average of 19 days. There was no bacteriological or clinical follow-up after discharge from hospital. Dosage schedule of chloramphenicol: The initial dose was 2 g daily (about 30-40 mg/kg body weight in most cases), administered in four separate doses until defeverscence occurred. Subsequently patients received either 1 g daily for 7 to 10 days, or a dose gradually reduced down to 1.5, 1.0 and 0.75 g. The drug was administered orally if possible. Blood clot culture: The blood ctot culture was performed as follows. Two millilitres of blood were placed in a dry sterile

Material and Methods This study was carried out from May to July 1972 at Kasturba Hospital for Infectious Diseases in Bombay, India. A total of 96 consecutively admitted cases were studied, 78 with typhoid fever and 18 with paratyphoid A fever. Four patients of the typhoid fever group were readmitted with a relapse. The diagnosis was made by blood culture in 97 cases (including one relapse). All 96 patients were males. Ages ranged from

Received: 21 October 1976

Dr. S.A. Kamat, Kasturba Hospital for Infection Diseases, Bombay, India; Dr. C. Herzog, Department of Paediatrics Royal Devon and Exeter Hospital, Exeter, England. Reprints: Dr. C. Herzog

Infection 5 (1977) Mr. 2

85

S. A. Kamat, C. Herzog: Typhoid: Clinical Picture and Response to ChloramphenicoI test tube, allowed to clot and the serum removed for Widal agglutination. 10-15 ml sterile oxen bile were then added to the clot and the mixture was incubated at 37 °C for 48 hrs. Cultures were plated on MacConkey's agar and subsequently incubated at 37 °C for 24 hrs. Corticosteroids and other drugs: Four cases with hyperpyrexia and/or a toxic crisis were given 20 mg prednisolone daily for four days, reduced down to 5 mg over six days. All patients routinely reveived multivitamin and lactobacilli preparations.

discharge. In one case S. typhi was isolated again after full clinical recovery, while the patient was still under treatment with chloramphenicol. Phage typing: Of the 40 strains of S. typhi examined 37 were phage type A, one phage type D 6 and two phage type E v Of the eight strains of S. paratyphi A examined three were phage type 1, four phage type 2 and one phage type 6.

Results Clinical manifestations

Signs

Two thirds of the patients reported to hospital within the first week, one third within the second week of illness. The onset of the disease was gradual in two thirds of the cases. In more than half of the 100 cases studied (including four relapses) the clinical picture was mild, as determined by a temperature not exceeding 39 °C and by the abscence of toxaemia and prostration. Symptoms: The symptoms encountered on admission are noted in Figure 1. The axillary temperature on admission was below 38 ° C in 21 cases, 3 8 - 3 9 °C in 51 cases, 39--40 °C in 27 cases and over 40 °C in one case.

Symptoms

Percentage among Typhoi~ Parat.A (n= 82) (n= 18)

Total (n= i00)

Fever

~

Headache

~

Bodyache

~

Cough

~

i

0

0

%

lO0

IOO

84.0

72,0

77.O

33,3

45%

48.8

27.8

Conjunctivitis ~

44%

45.0

39.0

Abdom.pain

~

43%

45.0

33.3

Constipation

~

34,0

27.8

Diarrhoea

~

Vomiting

~

Sore throat

~

Nausea~only)

~

82% 71%

33% 30% 26% 15% 10%

33.o

16.6

26.8

22.2

14,6

16.6

9.8

Ii.o 5.5

Eplstaxie

m

6%

6.i

Vertigo

~

4%

4.9

Chest pain

| 2%

2.4

Figure 1: Symptoms on admission among 100 cases o/ enteric fever (including [our relapses).

Clinical signs: The main signs observed on admission are summarized in Figure 2. Toxaemia was characterized by weakness, mental changes, toxic appearance (or typhoid state) and severe abdominal distension. In 16 cases a relative bradycardia was noted, as determined by pulse rates of less than 80, 100 or 120/min accompanied by temperatures of 38 °C, 39 °C or 40 °C respectively. Laboratory findings Clot culture: On admission S. typhi was isolated in 79 and S. paratyphi A in 18 cases. A second culture was performed in 73 cases (58 typhoid/15 paratyphoid A) before

86

Infection 5 (1977) Nr. 2

Coated tongue

Total (n= iOO)

~

51% 41%

Percentage among Typhoid Parat.A (n= S2) ~n= 18) 46.3

72.0

Toxaemia

~

Abdom. tenderness

~

Bronchitis

~

Enlarged liver

I~

19%

Enlarged spleen

~

19%

23.~2

Gurgling caecum

m

Relative bradycardia

m

16%

17%

Pharyngitis

m

Meteorism

m

43.6

27.7

33%

39.o

5.5

32%

35,3

16.5

17.O

27.S

19o5

5.5

17.O

ii.O

14%

13.4

16.6

13%

14.6

5.5

Guarding of abdomen

m 5%

6.1

Mental confusion

| 2%

2.4

Neningism

| 2%

2.4

Stomatitis

| 2%

2.4

Rose spots

|

2.4

Tonsillitis

] 1%

2%

1,2

Figure 2: Signs on admission among 100 cases of enteric fever (including four relapses).

Serological findings: On admission the Widal test was negative in 51o/0 of the typhoid fever cases (n = 78), in 8 9 % of the paratyphoid A fever cases and in two out of the three typhoid relapses examined. The Widal test remained negative in 12 out of 75 typhoid fever cases and in 15 out of 17 paratyphoid A fever cases studied. A rise of the typhoid O- and/or H-agglufinin titer could be observed in 35 typhoid fever cases, the typhoid 0 titer rising to 1 : 125 or higher and/or the typhoid H titer rising to 1 : 250 or higher in 29 cases. Bacteriological findings in stool and urine: F r o m the two consecutive stool cultures (n = 70/64) performed during therapy, S. typhi could be isolated in one case. Various strains of Shigella were isolated in 28 instances among 25 patients. F r o m the two consecutive urine cultures (n = 74/67) performed during therapy S. typhi was isolated in two cases. Leucocyte count: The leucocyte count on admission was below 3,000/mm~ in 4o/0, 3,000--5,000/ram 3 in 160/0, 5,000 to 10,000/mm~ in 710/0, and over 10,000/mm~ in 9°/o of the 96 cases examined. Two thirds of the patients had no eosinophits on admission, although 38o/o of these patients had intestinal parasites at the same time.

S. A. Kamat, C. Herzog: Typhoid: Clinical Picture and Response to Chloramphenicol Serum bilirubin and transaminases: During therapy the total serum bilirubin rose in three cases (n = 90) to 1.5 to 2.9 mgO/0 and the transarninases (SGOT and/or SGPT) in 36 cases (n = 90) to 4 2 - 1 1 2 U (normal ~ 40 U), Urine examination: Slight albuminuria was found in 55°/0 and marked albuminuria in 3 0 % of 94 cases on admission. Leucocyturia with more than 10 pus cells per microscopic field was noted in 30%. In 140/0 of the typhoid fever cases (n = 77) there were granular casts and in lO/0 erythrocytes in the sediment. Stool examination: Mucus, pus and/or blood were present in nine cases, in seven of them associated with Shigellae in the stool culture. Infection with intestinal parasites was present in 42 patients, with 13 double and one triple infection (25 Ascaris lumbircoides, 9 Trichuris trichiura, 5 Ancylostoma duodenale or Necator americanus, 14 Giardin lambia, 2 Trichomonas, 3 Entamoeba histolytica cysts). Response to therapy and course of the disease Defervescence: 98 cases were treated with chloramphenicol. In the 78 cases treated according to the dosage schedule described earlier (an average of 20 g over a period of 13 days) defervescence was achieved within 4.5 days on an average (Table 1), not including one fatal case and three patients with subfebrile temperature. In a further 16 cases which could not be evaluated for various reasons, normalisation of temperature was also obtained after an average of 4.5 days. I n four patients receiving prednisolone in addition the temperature dropped to normal within 12 to 24 hours. In one of these patients toxaemia persisted for four days, although fever responded quickly. Two abortive cases were discharged without any treatment. Table 1: Response o/ /ever to treatment with chloramphenicol* in 74 cases of enteric/ever No. of days taken for temperature to return to normal 1 2 3 4 5 6 7 8 9

day days days days days days days days days

Total Mean period of defervescence

No. of cases Total

~ Typhoid

2 8 19 12 10 10 6 5 2

2 7 17 11 7 7 4 5 2

74

62

4.5 days

4.4 days

Paratyphoid A

1 2 1 3 3 2

12 4.9 days

* Dose schedule: 40 mg/kg bodyweight until 2 days after defervescence, then half the dose for another 7-10 days. Adverse reactions due to chloramphenicol: A toxic crisis occurred in six of the 98 cases treated with chloramphenicol. One patient died (Case Report 1). Urticaria was ob-

served in one case which responded to antihistamine in spite of continuation of chloramphenicol. Complications and mortality: One seriously ill patient who developed a toxic crisis died finally. The cause of death of this single fatality could however not be established with certainty as no post mortem examination was performed. Case Report 1: A 27 year old patient was admitted with fever (39 °C), headache, constipation and a productive cough. He was first treated with penicillin for suspected pneumonia. After the positive blood clot culture for S. typhi, specific therapy with 2 g chloramphenicol daily was started. On the third day he developed a toxic crisis and subsequently became delirious and finally comatous. In the final stages he showed signs of encephalopathy such as stupor, rigidity of body and extremities, trembling and stereotype repetitive movements of the fingers, and incontinence of urine and stool. He developed bed sores. In spite of intensive care, he died on the ninth day on chloramphe~col - s t i l I comatous and febrile - with signs of cardiovascular collapse. Steroids were given on the final day. No signs of intestinal haemorrhage or perforation were observed. Complications occurred in 22 instances among 17 cases. One of the patients who suffered a toxic crisis developed deafness which improved only slowly during convalescence. In one patient, admitted with severe toxaemia and marked meningism, a psychotic mental state persisted during convalescence. One of seven cases with signs of peripheral neuritis was severely affected with ataxia and paraesthesia. A transient retention of urine occurred in one patient during the third week of illness. Extra systoles persisting for several days were observed in two patients. Labor pneumonia occurred in an elderly man. Signs of acute cholecystitis were noted in one patient in the third week of illness. A moderate intestinal haemorrhage occurred in two c a s e s - a t the beginning of the third week in one and at the end of the forth week of illness in the other. Milder complications inclnded pyodermia in one case and muscular pain in the calves in four cases. Signs of a slight haemolysis were noted in one case. Associated diseases: 42 patients showed infestation with intestinal parasites and 25 were infected with Shigella strains. One patient had more than 25o/0 eosinophils in the leucocyte count on two consecutive occasions and showed transient signs of bronchitis, probably connected with the finding of Ascaris lumbricoides ova in the stool. In all other cases none of the clinical features observed could be attributed with certainty to the above findings. Relapses: Of the 96 patients admitted initially, four patients in the typhoid fever group were re-admitted with a relapse after an afebrile interval of 18 to 23 days. Two of these relapses were again confirmed bacteriologically. Response to chloramphenicol was again very good.

Discussion E n t e r i c / e v e r in India: The majority of enteric fevers in India are caused by S. typhi (1, 26). The incidence of enteric fever due to S. paratyphi A is reported to vary

Infection 5 (1977) Nr. 2

87

S. A. Kamat, C. Herzog: Typhoid: Clinical Picture and Response to Chloramphenicol between 1.8o/0 (21), I4o/o (1) and 170/0 (26), compared with 19.6O/o in this study. S. paratyphi B trod C are reported only occasionally (1, 26). In accordance with this study various authors report the phage types A and E~ for S. typhi (26), and the phage types 1, 2, and 6 for S. paratyphi A (27) as being the most frequent in India. Clinical aspects: There is no clinical method of differentiating paratyphoid A fever from typhoid fever (9, 34) (Figure 1 and 2), although the former shows generally a milder course and fewer complications (9). Paratyphoid A fever is therefore included in the discussion unless stated otherwise. A synopsis of the clinical features in the present study compared with the findings in the literature is given in Table 2. Headache is usually accompanied by generalised aching and/or joint pain. Diarrhoea as an early symptom seems to be more frequent than constipation. Enlargement of the spleen is usually found in the majority of the cases and at an early stage of the disease exceeds the relative enlargement of the liver. Contrary to other studies (22, 32) no enlargement of the spleen was noted in the paratyphoid A fever cases. It is difficult to estimate the true incidence of rose spots in enteric fever, especially in dark-skinned patients (9, 29, 30). Incidences of 80/0 and 21--580/0 are reported from European countries and Chile, and of only 1--6o/o or none at all from Africa, India and

South East Asia (Table 2). Rose spots are found more frequently in paratyphoid fever, especially paratyphoid B (9). Unusual clinical features (6, 34), respectively wrong diagnoses on admission (3, 14, 18) have been reported in 13-180/0 of the cases in Egypt (34), South Africa (3) and India (6), in 2 9 % in Italy (14) and in 310/0 in England (18), compared with 350/0 in this study (Table 3). Laboratory findings: The only definite diagnostic criterion in enteric fever is the isolation of the organism from the blood (5, 9, 35). In this study the blood clot culture (9) was used, which generally gives more positive results than the usual blood culture methods (9, 33). The unsatisfactory results of the Widal test confirm previous experience in this centre and the experience of various authors in India (6, 28), Egypt (31) and in the United States (23) that too many false negative results are obtained with the Widal test and that it is um'etiabIe as a diagnostic criterion in both the early and later stages of the disease. The absence of leucocytosis, rather than lencopenia, seems to be an important feature of the blood picture in enteric fever (31). Leucocyte counts of less than 4,000-5,000/mm.~ are usually reported in only 20--45% of the cases (3, 6, 9, 10, 13, 15, 16, 20). A more reliable diagnostic sign is the absence of eosinophils in the differential blood count (2, 19, 31), especially in the presence of worm infestation.

Table 2: Clinical picture and mortality in enteric fever: comparison of clinical experience in various parts of the world. Author and year of publication

"~ ~N~ ~ E

Country

~

No. of cases

100

Clinical features in % of cases: Fever Headache Coug h Abdom. pain Toxaemia Nausea/vomiting Obstipation Abdom. tenderness Bronchitis Diarrhoea Enlarged liver Enlarged spleen Relative bradyeardia Rose spots Mortality (0/0):

* (98) 100 82 45 43 41 36 33 33 32 30 19 19 16 2 t

L-~ ~ ~"

m ~ ~"

eq ~ ~.

t---~ ~

t.-~ ~-

r-~ ~-

~ ~ ~

rq ~ ~

~, ~ ~-

~ ~ ~"

~ ~ ~"

,~ ,-~ ~

~ ~ ~

~e' ~"

~

N

M

c~

~

N

N

~

~

C)

N

~

~

N

159

98

240

43

267

101

100

74

95

139

340

360

507

300

(119)

(46)

(182)

(42)

(?)

(9t)

(87)

(?)

(22) (95)

(144) (262)

98 67 65 52

100 43

100 52 31 45 64 39 32

100 69 10 33 41 33 32

100 28 9 4 23 5

94 79

100 30 42 12 23 16 23

0

98 64 11 35 23 42 42 14 14 23 33 77 0 58

94 48

38 2I 0

94 75 35 70 54 25 15 61 56 43 6 18 12 5

10

13

5.4

0

37

54 50 50 5

* Cases proved culturally ** 45.3°/o for white 14.5% for colored people

88

Infection 5 (1977) Nr. 2

32

37 32 44 15

100 55 14 48 27 24 22

(403) (300)

100 90 86 76 73 54 79 84 64 43 25 64

75 78 37 34 7 24 38

100 75 56 90

33 64 85 39 8

19

20 69

45 11

7 44

36 16 31

84

32 1

57 68 51

19 46 14 20

21

0

0

**

46

19 16 22 31 14 29 74 29 4

1.5

2

2

0

2.1

5.8

5.6

12.7

0.6

2

21

22

41 15 39

S. A. Kamat, C. Herzog: Typhoid: Glinical Picture and Response to Chloramphenicol Table 3: Atypical clinical presentation of enteric [ever." comparison of the present study with findings from Italy (14), South Africa (3) and England (18).

Presumed diagnosis or atypical clinical picture on admission

Typhoid fever Suspected typhoid fever Fever of unknown origin

~ ,q =I +,~e" ~I~, ~ ~ ~ ~ ~

65

,L ~ ~

~" ~

44

9

i2

68

36

7

52

Response to chloramphenicol therapy: The introduction of chtoramphenicol in 1948 shortened the febrile stage of typhoid fever from several weeks to less than one week (36). In the present study the temperature returned to normal within an average of 4.5 days (Table 1). The effectiveness of chloramphenicol is still undisputed (7, 8). However, the recent spread of R-factor mediated chloramphenicol resistance throughout the world is alarming (8). It has so far been reported to be widespread in Mexico, India, Vietnam, Thailand, Cambodia, Formosa and Indonesia and sporadic cases have been reported in France, Spain, Greece, Israel, Algeria, Kuwait and Chile (8, 37). At the present time the aminopenicillins and cotrimoxazole are valuable alternative drugs (8, 12).

26

Influenza Malaria Sepsis Brucellosis Stomatitis Tonsillitis Bronchitis and/or pneumonia Pulmonary tuberculosis Gastroenterifis or colitis Dysentery Appendicitis Cholecystitis Amoebic liver abscess Hepatitis Urinary tract infection Nephritis Meningitis Varia

6 11

18

1

1

Total No. of cases

100

171

5 11 3

1

1 2

1

6

28 1

2 3

4 4 2

5

3 1

12 7 1

10 1

4 3 1

14 2 4 15" 159

74

* 5 pelvic infection, 2 melaena, 1 asthma 1 malabsorption, 1 intestinal obstruction, i hepatomegaly, 1 incomplete abortion, 1 bilharziosis, 1 encephalitis, 1 paraparesis

Treatment with chloramphenicol: The toxic crisis--an apparently drug-induced exacerbation of toxaemia and other symptoms of the disease, with fall of temperature and tendency to cardiovascular collapse (9, 24)--remains a danger in up to 100/0 of the cases (8). In this study six cases of toxic crisis were seen among 98 cases treated with chloramphenicol. This confirms previous findings of one of the authors (12). The haematotoxicity of chloramphenicol has been known for many years (17). No major haematological changes were observed in this study. An urticarial rash, a rare side-effect of chloramphenicol when administered orally (17), was noted in one case.

Complications and mortality: The rather mild course of the disease seen in this study corresponds to previous observations in this centre (12) and in other parts of India (21). The incidence of the major complications in typhoid fever found in this study and reported in the literature are summarized in Table 4. The introduction of ehtoramphenicol lowered the mortality rate of intestinal perforation from nearly 100% to generally less than 5 % (2, 9, 16, 24, 25). The mortality rate of intestinal haemorrhage may still be as high as 330/0 (9, 10, 21), although rates of 1.80/0 (25) and 6.60/o (24) have been reported in two large clinical studies. Cardiovascular failure with a mortality rate of 37--690/0 is t h e commonest fatal complication of typhoid fever in Africa (10, 34) and India (6, 21), which could partly be explained by the frequently poor general condition of the patients on admission to hospital, and is probably to a large extent caused by toxic myocarditis. The latter is reported to occur in 0.2-2°/0 (9, 11, 25, 30, 33) or even 21o/o (13) of typhoid fever cases. Pneumonia is mostly a superinfection not caused by typhoid bacilli (9). Muscular pain, frequently occurring in the calves, is due to a localized myosifis (9) and is sometimes difficult to differentiate from deep thrombosis. A transient psychosis (4, 9) may persist for weeks during convalescence. Deafness occurs in 0.8-40/0 (9, 20, 30), peripheral neuritis in 2--30/0 (9, 33) of typhoid fever cases. Relapses: The true relapse rate in this study cannot be stated as there was no follow-up. The relapse rate in patients treated with chloramphenicol seems to be higher than in patients not treated with this drug (8). It is detinitely lower in patients treated with aminopenicillins (7, 33) and propably also in those treated with cotrinoxazole (7). Isolation of Salmonella during treatment with ehloramphenieol: Medical textbooks mention that S. typhi disappears from the blood within a few hours of starting treatment with chloramphenicol. It is however possible to isolate the organism from the blood of patients receiving chloramphenicol (9, 35), as noted in one convalescent patient in this study.

Infection 5 (1977) Nr. 2

89

S. A. Kamat, C. Herzog: Typhoid: Clinical Picture and Response to Chloramphenicol Table 4: Complication rate, relapse rate and mortality rate in typhoid fever: comparison oJ clinical experience in various parts of the world. Percentage of cases

~ o~

~

Present study

India

(2) (6) (9) (10) (11)

ChiIe India Kenya Nigeria India

~

78

2.6 5.0 1.0 3.3 9.8 5.4

0.7 3.0 6.3 12.1 3.6

(t4) 1967 Italy

436 98 240 214 111 267 (24)*

1.9

0.7

(16) 1971 France

100 (10)*

8.0

1.0

5.0

1.7 3.9 21~1 0.2

0.8 0.4 1.9

1.2

1.3

0.6

(24) (25) (30) (33)

1965 1968 1962 1966 1963

1961 1967 1946 1964

Iran Chile USA EngIand

(34) 1970 Egypt

530 3036 360 469 300 (74)*

1.3

°

o

1.3

1.3

0.7 24.5 2.1 8.8 0.9

1.3

5.1

1.3

0.2

2.1 2.3

2.9 1.8 1.8

1.0

0.8 0.5

14.0 4.7 12.1

0.9 13.0 5.4 24.0 7.2

2.6

2.6

L1

0.7

6.7

1.5

4.0

14.0

2.0

0.2 1.9 0.4

10.8 8.5 12.5 18.3

3.6 0.7 t2.7 0.6

9.0

2.0

4.0 0.2

1.7

1.3 2.7 1.5

1.3

3.3

11.3 1.5

0.8 2.8

* Paratyphoid A or B fever cases included in the total numberof cases

A cknowtedgement We thank Dr. R. S. Deshpande, Medical officer, Kasturba Hospital for Infectious Diseases, Bombay, for permission to undertake the study, and the resident nm-sing and laboratory staff of the Kasturba Hospital for their help and cooperation. The phage typing was kindly carried out by Prof. K. B. Sharma, Salmonella Phage Typing Centre, Department of Microbiology, Lady Hardin Medical College, New Delhi.

Literature 1. Basu, S., Dewan, M. L., Suri, J. C.: Prevalence of Salmonella serotypes in India: a 16-year study. Bull. World Health Organ. 52 (1975) 331-336. 2. Borgono, 1. M., Pearson, E.: Fiebbre tifoidea y paratifoidea: analisis clinico y de laboratorio de un brote estacional. Rev. Med. Chil. 93 (1965) 145-151. 3. Chatmers, 1. M.: Typhoid fever in an endemic area: a great imitator. S. Aft. Med. J. 45 (1971) 470--472. 4. Editorial: Psychiatric symptoms in typhoid fever. Brit. med. J, (1973/II) 436-437.

5. Gilman, R.H., Terminel, M. Levine, M.M., HernandezMendosa, P., Hornick, R. B.: Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose-spot cultures for recovery of Salmonella typhi in typhoid fever. Lancet (1975H) 12111213. 6. Gulati, P. D., Saxena, S.N. Gupta, P. S., Chuttani, H. K.: Changing pattern of typhoid fever. Amer. J, Med. 45 (1968) 544-548. 7. Herzog, C.: Klinik und Chemotherapie des Typhus abdominatis. Vergleich yon 100 mit Chloramphenicol behandelten

90

Infection 5 (1977) Nr. 2

konsekutiven Fiillen aus Bombay, Indien (1972), mit neueren Erkenntnissen aus der Literatur. Dissertation, Basel 1975.

8. Herzog, C.: Chemotherapy of typhoid fever: a review of literature. Infection 4 (1976) 166-173. 9. Huckstep, R.L.: Typhoid fever and other Salmonella infections. Livingstone, Edinburgh 1962. 10. Ikeme, ,4. C., Anan, C. 0.: A clinical review of typhoid fever in Ibadan Nigeria. J. trop. Med. Hyg. 69 (1966) 15-21.

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Typhoid: clinical picture and response to chloramphenicol. Prospective study in Bombay (1972).

S. A. Kamat, C. Herzog Typhoid: Clinical Picture and Response to Chlorarnphenicol Prospective Study in Bombay (1972) Summary: The clinical picture of...
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