Enteric Fever: A Review of Ninety Cases

Bienvenido D. Alora, M.D., D.T.M. & H.* and Pamela Lloren,M.D.**

(*Associate Professor and Chief, Section of Infectious Diseases, Department of Medicine, Faculty of Medicine and
Surgery; **Senior Resident, Dept. of Medicine, STUH)

SUMMARY

Ninety cases of enteric fever admitted in tile Santo Tomas University Hospital, Clinical Division from 1973
to 1977 were reviewed. Fifty five percent were males and the majority was in the first and second decades of life.
The clinical and physical features were discussed. Fever, toxemia, and relative bradycardia were the most
common symptoms.
The different laboratory findings, complications, and management were presented. [Phil J Microbiol Infect
Dis 1980; 9(2):118-128]

Key Words: enteric fever, Salmonella typhi, Salmonella paratyphi, salmonellosis

INTRODUCTION

Enteric fever is essentially a human infection and the invariable source is either a patient
suffering from a mild form, or a chronic carrier. Salmonella typhi, the most serious cause of
enteric fever, affects mainly the lower part of the ileum where it enters the lymphoid follicles.
These undergo necrosis and ulceration, the mesenteric lymph nodes become infected and the
salmonella invades the bloodstream via the thoracic duct. Bacteremia begins during the first week
and may continue up to the fourth week. During this phase, the bone marrow, spleen, kidney,
liver, and gallbladder may become infected. The gallbladder may re-infect the intestines causing
further acute infla mmation of the lymphoid follicles. Salmonella paratyphi may produce
ulceration lower down in the intestines and these organisms pass through the feces resulting in
contamination of the water and food supply by carriers or flies which are the usual transmission
of infection.(Figure 1)

Figure 1. Pathophysiology of Enteric Fever

 Medical history attests that enteric fever has existed for several centuries. Willis made the
first description of the epidemic typhoid in 1659. Gerhard, in 1837, was the first to clearly
differentiate typhoid from typhus fever. In 1880, Eberth discovered the typhoid agglutinins and
its diagnostic application. In 1896, Archard and Bensaude were the first to isolate S. paratyphi
and other salmonella. In 1948, Woodward et al first used Chloramphenicol against typhoid fever
(Table 1).

Table 1. Historical Background

Willis (1659) first description of epidemic typhoid

Gerhard (1837) first distinct differentiation of typhoid from typhus fever
Eberth (1880) discoverer of typhoid bacillus
Widal (1895) discoverer of typhoid agglutinins and its diagnostic applications
Archard and Bensaude (1896) discoverer of paratyphoid bacillus and other salmonellae
Woodward et al first used chloramphenicol vs. typhoid fever

Enteric fever is still one of the major health problems in the Philippines today. A total of
150 cases admitted at the STUH-CD were diagnosed as enteric fever. Ninety of the eases were
selected for this review upon fulfilling the following criteria: first, clinical features of prolonged
pyrexia of more than one week duration, toxemia, or pulse fever disproportion, second, positive
Widal test, or positive bacteriologic culture in the blood, urine or stool or a histologic picture
compatible with enteric fever, and third, favorable response to treatment against enteric fever
(Table 2)
It is the objective of this paper to determine the incidence the clinical and laboratory
features, complications and management of enteric fever in our hospital.

Table 2. Criteria

Clinical features
a. Prolonged pyrexia (more than one week duration)
b. Toxemia
c. Pulse and fever disproportion
d. Splenomegaly and/or hepatomegaly
e. Rose spots
Laboratory Features
a. Positive Wida1 Test
b. Positive bacteriologic culture in the blood, stoo1, or urine
c. Histopathologic picture
Favorable response to medications against enteric fever

Table 3 shows the age and sex distribution. 55% were males and the majority was in the
first and second decades of life.

Table 3. Age and Sex Distribution

Age Male Female Total

10 - 19 18 16 34 (38%)
20 - 29 19 15 34 (38%)
30 - 39 7 4 11 (12%)
40 - 49 5 4 9 (10%)
50 - above 1 1 2 (2%)
Total 50 (55%) 40 (45%) 90 (100%)
 Table 4 illustrates the different clinical manifestations. Fever was the most constant
symptom in our series, Headaches and chills were present hi 53%, abdominal pain 48%, anorexia
in 44%, malaise in 33%, vomiting in31%, diarrhea in 29%. Jaundice was seen in 15.5% of the
patients as corn-pared to the 50% reported by Perez et al in 1973. Constipation and nausea were
seen in 12% and disorientation in 3%.

Table 4. Clinical Manifestations

No. Percent
Fever 90 100%
Headache 48 53%
Chills 48 53%
Abdominal Pain 43 48%
Anorexia 40 44%
Malaise 30 33%
Vomiting 28 31%
Diarrhea 26 29%
Jaundice 14 15.5%
Constipation 11 12%
Nausea 11 12%
Disorientation 3 3%

Table 5 presents the various physical features in our series. Pyrexia was present in all.
The type, severity, and duration of pyrexia were not helpful in the diagnosis. The temperature was
usually high (39.5O C) but it was sometimes moderate (37.7O C) to (39O C) or even subnormal (less
than 37.7°C).
Toxemia was seen in 88% of the cases. Foreign authors reported a lower incidence of 34-
45.6%. Relative bradycardia was present in 73%. Development of tachycardia in some patients
indicated complications such as hemorrhage or other associated infections. Abdominal tenderness
was present in 46.6%; Lucindo et al reported a similar incidence while Perez showed a higher
incidence of 59%. Hepatomegaly was present in 26.6% and splenomegaly, in 12% as compared
to Perez with a higher incidence of 31% and 27%. Congested throat was seen in 11%; CVA
tenderness in 3%, rose spots and stupor in 2% each. Lucindo reported a lower incidence of rose
spots, 0.9%.

Table 5. Physical Features

No. Percent
Fever 90 1,00%
Toxemia 79 88%
Relative bradycardia 66 73%
Abdominal tenderness 41 46.6%
Hepatomegaly 24 26.6%
Splenomegaly 11 12%
Congested throat 10 11,%
CVA tenderness 3 3%
Rose spots 2 2%
Stupor 2 2%

Table 7 shows the results of laboratory examination and procedures in this series. Widal
test was positive in 63% of cases at 1:160 level adequate for diagnosis of enteric fever. There
were some patients where the Widal test was not done. Blood culture was positive in only one
case. Liver biopsy done in two patients showed granulomatous necrosis of parenchymal
degeneration compatible with enteric fever. Hb level of less than 10 gms was noted in 28 patients
or 31%. Sixty four percent showed normal wbc, 26.7% had leukocytosis, and 4% showed
leukopenia. Lymphocytosis was noted in 65.5% and thrombocytopenia in 3% or 3 patients. The
liver function tests showed varying degrees of bilirubin levels, in 16 patients it was over 2 mgs,
more of the direct type. The serum transaminases done in 10-20% of the cases were not
considerab1y elevated as compared to viral hepatitis with levels beyond 500 units. Urinary
findings showed mild pyuria and cylindruria in 3% respectively and bacteriuria in 1%.

Table 6. Laboratory Features

No. Percent
A. Widal test
Positive 57 64%
Negative 12 36%
B. Bacteriologic Studies
Blood culture
Positive 1
Negative 10
Stool culture Negative 11 100%
Urine culture Negative 4 100%
C. Liver biopsy Positive 4 100%
D. Blood test
Hemoglobin (less than 10 gms) 28 31%
WBC
Normal 58 64 %
Leucocytosis (more than 10,000/cu mm) 24 26%
Leucopenia (less than 5,000/cu mm) 4 4%
Lymphocytosis (more than 30%) 59 65.5%
Thrombocytopenia (less than 160,000/cu mm) 3 3%
D. Liver Function Tests
S. Bilirubin (above 2 mg%) 16 18%
SGOT (above 50 units) 13 14.4%
SGPT (above 50 units) 9 10%
F. Urinary Findings
Pyuria (more than 4 cells/HPF) 3 3%
Cylindruria 3 3%
Bacteriuria 1 1%

Table 7 discloses the different complications encountered in the series. Hemorrhage

occurred in 25.5% mostly affecting the GI tract. Pangan reported a similar incidence of 26% in
1971 while Perez showed a lower incidence of 21% in 1973. Pneumonitis was noted in 18
patients or 21%, ileus and mechanical obstruction 1% each. Perforation developed in one case
with detection of pneumoperitoneum by x-ray. This patient eventually succumbed and
postmortem showed hyperplasia of Peyer's patches with enlarged mesenteric pericolic,
portohepatic lymph nodes. Pangan reported a 28% mortality rate in patients with perforation. One
patient developed psychosis and another had an abortion during the course of the illness.

Table 7. Complications

No. Percent
Intestinal Hemorrhage 23 25.5%
Pneumonitis 18 2.1%
Ileus 1 1%
Mechanical Obstruction 1 1%
Perforation 1 1%
Psychosis 1 1%
Abortion 1 1%

Table 8 presents the treatment of enteric fever. All of the patients were managed
medically. Twenty four or 26.6% responded to cotrimoxazole, 17 or 19% to chloramphenicol
alone, 15 or 17% to a combination of chloramphenicol and cotrimoxazole, 14 or 16% to
chloramphenicol + cotrimoxazole with steroids. The rest responded with either chloramphenicol
or cotrimoxazole together with other antibiotics or steroids, General supportive management of
the patient supplemented antibiotic therapy. Bed rest extending to early convalescence was
essential. All patients were hydrated and only 8 or 9% received blood transfusion. Laxatives and
promiscuous use of enemas were avoided because of the danger of perforation or hemorrhage of
the intestinal lesions. Ambulation was initiated gradually to avoid undue fatigue and exertion.

Table 8. Management

No. Percent
A. Antibiotics
Cotrimoxazole 24 26.6%
Chloramphenicol 17 19%
Chloramphenicol + Cotrimoxazole 15 17%
Chloramphenicol + Cotrimoxazole + Steroids 5 5.5%
Chloramphenicol + Other Antibiotics 5
Cotrimoxazole + Steroids 5
Cotrimoxazole + Other Antibiotics 5
Chloramphenicol + Cotrimoxazole + Other Antibiotics 2
Ampicillin 1
B. Supportive
Blood transfusion 8 9%

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