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Dr Mahesh H Ahirrao et al JMSCR Volume 07 Issue 03 March 2019 Page 696
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2019
Enteric fever - Clinical presentation, lab parameters, Complications and
Sensitivity pattern in a tertiary care centre in Rural Maharashtra
Authors
Dr Mahesh H Ahirrao1, Dr Bhagyashri Ahirrao2, Dr Jagdish Pakhare3,
Dr Nandkumar V Dravid4, Dr Karuna Shejwal5, Dr Ashish Patil6
1Associate Professor,3Professor, 5Resident, Department of Pediatrics ACPM Medical College Dhule.
2Assistant Professor, 4Professor and HOD, Department of Pathology ACPM Medical College Dhule.
6Assistant Professor Department of Microbiology ACPM Medical College Dhule
Corresponding Author:
Dr Bhagyashri Ahirrao
Assistant Professor, Department of Pathology ACPM Medical College Dhule, India
Abstract
Introduction: Enteric Fever is endemic in South East Asia and poses a significant health problem in developing
countries including India. Though treatable, enteric fever is known to cause potentially life threatening complications
such as encephalopathy and enteric perforations. Diagnosis and management of enteric fever in pediatric age group
pose several problems because of non- specific symptomatology. We conducted this prospective study to analyze
clinical presentation, lab parameters, Sensitivity pattern and Complications in pediatric patients admitted with the
diagnosis of enteric fever.
Materials and Methods: This was a prospective cohort study in which pediatric patients having enteric fever were
included on the basis of a predefined inclusion and exclusion criteria. The study was conducted in a tertiary care
medical college situated in a rural area. Informed consent was obtained from the guardians of the cases. Detailed
history and demographic details were noted and thorough clinical examination was done in all the cases. Complete
blood count, blood culture and sensitivity and Widal test was done in all the cases. Complications during hospital stay
were also noted down. SSPE 16 version software was used for statistical analysis. P value less than 0.05 was taken as
statistically significant.
Results: Out of 80 studied cases there were 46 (57.50%) males and 34 (42.50%) females with a M:F ratio of 1: 0.73.
The most common sign was fever which was present in all (100%) the cases. The other signs and symptoms were
headache (33.75%), high grade fever (28.75%), vomiting (28.75%) abdominal pain (21.25%) and chills (16.25%). On
clinical examination isolated hepatomegaly and splenomegaly was present in 16 (20.00%) and 7 (8.75%) patients
respectively whereas hepatosplenomegaly was present in 14 (17.50%) patients. Leukopenia was seen in 26 (32.50%)
patients whereas leukocytosis was present in 7 (8.75%) patients. thrombocytopenia and deranged hepatic function
tests were seen in 13 (16.25%) and 7 (8.75%) patients respectively. Blood culture was positive in 39 (48.75%)
patients. Widal test was found to be positive in 41 (51.25%) patients.75 (93.75%) patients responded well to
administration of antibiotics. 5 (6.25%) patients developed complications such as meningeal signs (3.75%), bleeding
diathesis (1.25%)and enteric perforation (1.25%).
Conclusion: Enteric fever is endemic in developing countries including India. Varied symptomatology makes its
diagnosis difficult particularly in pediatric age group. Delayed diagnosis may lead to complications such as
encephalopathy, bleeding diathesis and enteric perforation.
Keywords: Enteric Fever, Encephalopathy, Enteric perforation, Culture and Sensitivity.
www.jmscr.igmpublication.org
Index Copernicus Value: 79.54
ISSN (e)-2347-176x ISSN (p) 2455-0450
DOI: https://dx.doi.org/10.18535/jmscr/v7i3.127
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Introduction
Enteric Fever (EF) is a common health problem in
developing countries of South East Asia including
India. more than 2/3rd of all the cases of enteric
fever come from India, china, Bangladesh, Nepal
and Vietnam1. Unhygienic conditions and poor
sanitation facilities are important are the most
important risk factors for transmission. EF is
primarily caused by gram negative enteric bacillus
belonging to family enterobacteriaceae. The other
common organisms which may cause EF include
salmonella paratyphi A, B and C2. EF particularly
in pediatric age group, may present with varied
presentation and hence early diagnosis requires a
high index of suspicion.
The mode of transmission is generally feco-oral
route and the incubation period is usually 1-2
weeks. The patients usually present with signs and
symptoms such as fever, abdominal pain, rash,
splenomegaly, relative bradycardia and anorexia.
Delayed diagnosis and inadequate treatment may
result in life threatening complications such as
encephalopathy, enteric perforations, toxemia,
disseminated intravascular coagulopathy (DIC)
and myocarditis. One must also be aware of
atypical presentation of typhoid fever which may
include severe headache, lobar pneumonia,
osteomyelitis, cholecystitis, arthralgia and
neurological manifestations such as altered
sensorium and abnormal movements (chorea) 3.
A high index of suspicion, proper history and
clinical examination is most important for the
diagnosis of enteric fever because the sensitivity
and specificity of the available diagnostic tests
vary greatly as reported by various studies across
the literature. The most specific test for the
diagnosis of EF is blood culture and isolation of
bacteria in patients presenting with clinical picture
suggestive of EF is considered diagnostic of
enteric fever4. Within the first week of
presentation blood culture may turn out to be
positive and is diagnostic in majority of the cases.
Widal test is neither sensitive nor specific and
hence can’t be relied upon solely5. Other
serological tests such as indirect
haemagglutination test and ELISA for IgG and
IgM antibodies have reported to be having varying
sensitivity and specificity6. The investigations
such as bone marrow culture has got high
sensitivity but the invasive and painful nature of
the test preclude its use as a routine investigative
procedure for the diagnosis of EF. The laboratory
features such as leukopenia and increased ESR
may suggest EF but are non-specific. Presence of
thrombocytopenia, elevated prothrombin and
activated partial thromboplastin time combined
with decreased fibrinogen level may suggest the
possibility of potentially life threatening DIC7.
Management of EF includes general measures
such as prevention of dehydration, maintenance of
electrolyte balance and management of fever. An
appropriate antibiotics in proper doses on the basis
of culture sensitivity report is the cornerstone of
therapy. Chloramphenicol and ampicillin which
were used in past are hardly effective nowadays
and fluoroquinolones, azithromycin and
cephalosporins (ceftriaxone or cefixime) are very
effective in treatment8.We conducted this
prospective study to analyze clinical features,
laboratory parameters, sensitivity pattern and
complications in pediatric patients admitted with
enteric fever.
Materials and Methods
This was a prospective study conducted in the
department of pediatrics of a tertiary care medical
college situated in the rural area of Maharashtra
State. The patients less than 18 years (pediatric
age group) admitted with the primary diagnosis of
enteric fever on the basis of a predefined inclusion
and exclusion criteria. Informed consent was
obtained from the guardians of the patients. The
demographic details such as age, gender and
address of all the patients were recorded. A
detailed history about the duration of illness,
presenting complaints and history of similar
illness in family members was also noted down. A
through clinical examination was done in all the
cases. Any history of receiving antibiotics was
asked for. Any history to drugs such as
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fluroquinolnes, ceftriaxone and azithromycin was
asked for. Blood samples were collected for
complete blood count, electrolytes, erythrocyte
sedimentation rate, WIDAL and blood culture.
Antibiotics were started after collection of blood
samples. Presence of electrolyte imbalance was
corrected by appropriate measures. Clinical
improvement was studied by repeated clinical
examination. Presence of signs and symptoms
suggestive of complications were specifically
looked for. further specific tests were done in
patients who showed signs of complications such
as coagulation profile in patients presenting with
bleeding manifestation and imaging in cases
suspected to be having complications such as
perforation. Appropriate surgical consultation was
sought if needed. If required antibiotics were
switched on the basis of culture and sensitivity
reports. SSPE 16 version software was used for
statistical analysis and p value less than 0.05 was
taken as statistically significant.
Inclusion Criteria
1. Patient admitted with clinical features
suggestive of enteric fever.
2. Age less than 18 years.
3. Guardians have given informed consent to
be part of the study.
4. Patients confirmed to be having enteric
fever on the basis of investigations.
Exclusion Criteria
1. Age more than 18 years.
2. Patients whose guardians refused consent.
3. Patients in whom alternate diagnosis was
confirmed.
Results
Out of the 80 pediatric patients included in this
study there were 46 (57.50%) males and 34
(42.50%) females with a M:F ratio of 1:0.73
Figure 1: Gender Distribution of the studied
cases.
The analysis of the cases on the basis of parents’
socio-economic status showed that the maximum
number of patients belonged to lower socio-
economic status (56.25%). This was followed by
patients from lower middle class (28.75%) and
middle class (15%). There was no patient
belonging to upper middle and upper class.
Table 1: Gender wise Socio-Economic status of the studied cases
Socio-Economic Status
Male
Female
Total
%
Upper
-
-
-
-
Upper Middle
-
-
-
-
Middle
8
4
12
15.00%
Lower Middle
16
7
23
28.75%
Lower
22
23
45
56.25%
Total
46
34
80
100.00
The analysis of the patients on the basis of age
groups showed that the most common affected age
group was found to be between 5-10 years
(57.50%) followed by 15-18 years (23.75%) and
11-15 years (15.00%). There were only 3(3.75%)
cases diagnosed to be having enteric fever before
5 years of age. The mean age of males and
females was found to be 9.47 +/- 4.61 and 9.72 +/-
4.49 respectively. There was no statistically
significant difference in the mean age of the males
and females (P=0.80).
46
34
Males
Females
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Table 2: Age groups of the studied cases
Age Group
Males
Females
No Of Patients
Percentage
No Of Patients
Percentage
Upto 5 yrs of age
2
2.50%
1
1.25%
5-10 years
26
32.50%
20
25.00%
11-15 years
7
8.75%
5
6.25%
15-18 years
11
13.75%
8
10.00%
Total
46
57.50%
34
42.50%
Mean Age: 9.47 +/- 4.61
Mean Age: 9.72 +/- 4.49
P= 0.80 (Not Significant)
The analysis of signs and symptoms of the
patients showed that the most common sign in the
studied cases was fever which was present in all
80 cases (100%). The other common signs or
symptoms seen in studied cases were headache
(33.75%), high grade fever (28.75%), vomiting
(28.75%), abdominal pain (21.25%) and chills
(16.25%). isolated hepatomegaly and
splenomegaly was seen clinically in 16 (20%) and
7 (8.75%) respectively whereas
hepatoplenomegaly was seen in 14 (17.50%)
patients. Pallor was present in 8 (10%) patients. 5
(6.25%) patients were found to have toxic look
and meningeal signs were present in 3 (3.75%)
patients. Abdominal guarding and tenderness was
present in 1 (1.25%) patient.
Table 3: Signs and Symptoms of the studied cases
Signs and Symptoms
No of Patients
Percentage
Fever
80
100 %
Headache
277
33.75%
High grade fever
23
28.75%
Vomiting
23
28.75%
Abdominal Pain
17
21.25%
Chills
13
16.25%
Hepatomegaly
16
20.00%
Splenomegaly
7
8.75%
Hepatosplenomegaly
14
17.50%
Pallor
8
10.00%
Toxic Look
5
6.25%
Meningeal Signs
3
3.75%
Abdominal guarding and tenderness
1
1.25%
The analysis of laboratory parameters showed that
anemia was present in 11 (13.75%) children. The
other abnormalities on complete blood count were
found to be leukopenia which was seen in 26
(32.50%) patients whereas leukocytosis was seen
in 7 patients (8.75%). Neutropenia and
neutrophilia was present in (37.50%) and
(27.50%) patients respectively whereas
eosinopenia and eosinophilia was present in
(40.00%) and (26.25%) patients respectively.
Evidence of thrombocytopenia was present in 13
patients (16.25%). Significantly raised Widaltiters
were seen in 41 (51.25%) patients.
Table 4: Laboratory Parameters in studied cases
Laboratory Parameters
Values
No Of Patients
Percentage
Hemoglobin
Anemia (Hb< 11 gm %)
11
13.75%
Normal
69
86.25%
Total Leukocyte count
Leukocytosis
7
8.75%
Leukopenia
26
32.50%
Neutrophil Count
Neutrophilia
22
27.50%
Neutropenia
30
37.50%
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Eosinophil count
Eosinophilia
9
11.25%
Eosinopenia
32
40.00%
Platelets
Thrombocytopenia
13
16.25%
Normal
67
83.75%
Liver Function Test
Raised Bilirubin
3
3.75%
Raised Liver Enzymes
7
8.75%
WIDAL titers
Significantly Raised
41
51.25%
Not Significantly Raised
39
48.75%
Blood Culture
Positive For Salmonella
39
48.75%
No Growth
41
51.25%
Analysis of blood culture for growth of salmonella
species showed that out of 80 patients in whom
blood culture was done 39 (48.75%) patients had a
positive blood culture for salmonella whereas
remaining patients were found to have no growth
on culture (51.25%).
Figure 2: Blood culture for presence of salmonella
The analysis of antibiotic sensitivity patterns of
the studied cases showed that all culture positive
organisms were sensitive to ceftriaxone (94.87%).
The other drugs to which organisms were found to
be sensitive were found to be cefixime (92.31%),
ciprofloxacin (89.74%%) ofloxacin (92.31%) and
azithromycin (82.05%). Comparatively less cases
were found to be sensitive to drugs such as
amoxicillin (61.54%), chloramphenicol (38.46%)
and trimethoprim-suphamethaxazole (28.21%).
Figure 3: Sensitivity Patterns of the culture positive cases
0
10
20
30
40
50
60
Positive
Negative
39
51
Blood culture
0
5
10
15
20
25
30
35
40
Ceftriax
one
Cefixim
e
Ciproflo
xacin
Ofloxaci
n
Azithro
mycin
Amoxici
llin
Chlora
mpheni
col
TMP+SZ
Resistant
2
3
4
3
7
15
24
28
Sensitive
37
36
35
36
32
24
15
11
37
36
35
36
32
24
15
11
2
3
4
3
7
15
24
28
Sensitivity Patterns
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All patients were successfully treated by
appropriate antibiotics and out of 80 studied cases
75 patients could be discharged after 5 days of
antibiotic therapy and asked to continue
antibiotics and remain in follow up for 2 weeks.
Out of remaining 4 patients 3 (3.75%) developed
signs of meningeal irritation and 1 patient (1.25%)
developed abdominal guarding and rigidity.
Bleeding diathesis was seen in 1 patient (1.25%)
who was treated by transfusion of fresh blood and
fresh frozen plasma (FFP). Erect X-ray abdomen
was done which showed gas under diaphragm and
hence in view of enteric perforation the patient
was shifted to surgery. There was no mortality in
any of the studied cases during the period of
study.
Figure 4: Complications in the studied cases
Discussion
This study comprised of 80 patients of pediatric
age group who had been admitted with enteric
fever. Out of these 80 cases there was a male
predominance with a M:F ratio of 1:0.73.
Maheshwari V et alconducted a cross sectional
study of 163 clinically suspected patients of
enteric fever9. Out of these 163 studied cases there
were 89 males (54.60%) and 74 females
(45.40%). Similar male preponderance was
reported by Malik GM et al10 and Mathura KC et
al11 Though the exact cause of this male
preponderance is not known the authors such as
Khan M et al proposed that there are sex-linked
differences in the degree of natural exposure of
Peyer’s patches to S. typhi as well as sexual
dimorphism in host inflammatory response
patterns which may be responsible for increased
incidence and complications (perforation) of
enteric fever in males as compared to females12.
The mean age of the studied cases in our patients
was found to be 9.51 years and the most common
affected age group was found to be between 5-10
years. Iftikhar et al conducted a study of pediatric
patients with enteric fever to find out frequency of
various complications13. The authors found that
Mean age of children was 7.2±3.38 and majority
94 (52.2%) of the children were 5-10 years
old. The authors such as Akullian A et al14 and
Comeau JL15 et al studying enteric fever in
pediatric age group found the mean age of
affected cases to be 8.4 years and 7.5 years. Mean
age of cases in our study was found to be
comparable to the mean age of cases in all these
studies.
In our study fever (100%) headache (33.75%),
high grade fever (28.75%), vomiting (28.75%),
abdominal pain (21.25%) and chills (16.25%)
75
3
1
1
5
Complications
No complication
Meningeal Signs
Perforation
Bleeding Diathesis
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were the common presenting complaints. Dheer G
et al in their study of children with enteric fever
found fever, vomiting, cough anorexia, diarrhea,
abdominal pain, hepatomegaly, splenomegaly and
coated tongue to be common signs and symptoms
of enteric fever in children16. The author
recommended that enteric fever should be
considered in the differential diagnosis of febrile
patients with abdominal symptoms. Fever and
abdominal pain were found to be common
complaints in pediatric patients with enteric fever
as reported by Mweu E et al17.
The investigations in studied cases showed
presence of abnormalities such as leukopenia
(32.50%), thrombocytopenia (16.25%), raised
hepatic enzymes (8.75%) and bilirubin (3.75%).
Khosla SN et al conducted a study to know the
hematological abnormalities in patients with
enteric fever and found that anemia, leucopenia,
eosinopenia, thrombocytopenia and sub-clinical
disseminated intravascular coagulation were some
of the common hematological abnormalities seen
in such patients18.
In our study blood culture was found to be
positive in 39 (48.75%) patients and sensitivity
patterns of the organisms showed that they were
mostly sensitive to ceftriaxone (94.87%) cefixime
(92.31%), ciprofloxacin (89.74 %%) ofloxacin
(92.31%) and azithromycin (82.05%). The
organisms were found to be relatively resistant to
antibiotics such as chloramphenicol, amoxicillin
and trimethoprim-sulphamethaxazole
combination. Similar sensitivity patterns were
reported by the authors such as Gidvani CH et al
who on the basis of culture and sensitivity
reported that 100% cases were sensitive to
ciprofloxacin followed by gentamicin (84.9%),
cephalexin (83.6%), furazolidine (36.6%),
trimethoprim-sulfamethoxazole (34.1%),
chloramphenicol (34.0%) and amoxycillin
(23.8%)19.
Finally the analysis of complication rates in our
study showed that out of 80 studied cases 75 ()
cases recovered completely without any overt
complications. 5 patients developed complication
such as meningeal signs (3/5), bleeding diathesis
(1/5) and enteric perforation (1/5) and were
treated accordingly. There was no mortality in any
of the studied cases during study period. Similar
complication rates were reported by Chiu CH et al
who reported complications such as intestinal
perforation (3%), rectal bleeding (3%), ascites or
pleural effusion (4%), and meningitis (1%)in
pediatric patients with enteric fever20.
Conclusion
Enteric fever is one of the major health problems
of developing countries including India.
Possibility of EF must be considered in any
patient presenting with fever and abdominal
symptoms. Early diagnosis and proper
antimicrobial treatment is required as delay in
antimicrobial treatment may lead to severe and
life threatening complications such as
disseminated intravascular coagulation, meningitis
and enteric perforation.
Conflict of Interest: None
References
1. Date KA, Bentsi-Enchill AD, Fox KK,
Abeysinghe N, Mintz ED, Khan MI,
Sahastrabuddhe S, Hyde TB; Centers for
Disease Control and Prevention (CDC).
Typhoid Fever surveillance and vaccine
use - South-East Asia and Western Pacific
regions, 2009-2013.
2. Bhan MK, Bahl R, Bhatnagar S. Typhoid
and paratyphoid fever. Lancet. 2005 Aug
27-Sep 2;366(9487):749-62.
3. Sejvar J, Lutterloh E, Naiene J, et al.
Neurologic manifestations associated with
an outbreak of typhoid fever, Malawi--
Mozambique, 2009: an epidemiologic
investigation. PLoS One. 2012;7(12):
e46099.
4. Dance D, Richens JE, Ho M, Acharya G,
Pokhrel B, Tuladhar NR. Blood and bone
marrow cultures in enteric fever. J Clin
Pathol. 1991;44(12):1038.
Dr Mahesh H Ahirrao et al JMSCR Volume 07 Issue 03 March 2019 Page 703
JMSCR Vol||07||Issue||03||Page 696-703||March
2019
5. Willke A, Ergonul O, Bayar B. Widal test
in diagnosis of typhoid fever in
Turkey. Clin Diagn Lab Immunol.
2002;9(4):938-41.
6. Choo KE, Davis TM, Ismail A, Tuan
Ibrahim TA, Ghazali WN. Rapid and
reliable serological diagnosis of enteric
fever: comparative sensitivity and
specificity of Typhidot and Typhidot-M
tests in febrile Malaysian children. Acta
Trop. 1999 Mar 15;72(2):175-83.
7. Butler T, Bell WR, Levin J, Linh NN,
Arnold K. Typhoid fever. Studies of blood
coagulation, bacteremia, and endotoxemia.
Arch Intern Med. 1978 Mar;138(3):407-
10.
8. Thompson CN, Karkey A, Dongol S, et al.
Treatment Response in Enteric Fever in an
Era of Increasing Antimicrobial
Resistance: An Individual Patient Data
Analysis of 2092 Participants Enrolled into
4 Randomized, Controlled Trials in
Nepal. Clin Infect Dis. 2017;64(11):1522-
1531.
9. Maheshwari V, Kaore NM, Ramnani VK,
Sarda S. A Comparative Evaluation of
Different Diagnostic Modalities in the
Diagnosis of Typhoid Fever Using a
Composite Reference Standard: A Tertiary
Hospital Based Study in Central India. J
Clin Diagn Res. 2016;10(10):DC01-DC04.
10. Malik GM. Enteric Fever in asir region,
southern of saudi arabia. J Family
Community Med. 1994;1(1):35-9.
11. Mathura KC, Gurubacharya DL, Shrestha
A, Pant S, Basnet P, Karki DB. Clinical
profile of typhoid patients. Kathmandu
Univ Med J (KUMJ). 2003Apr-
Jun;1(2):135-7.
12. Khan M. A plausible explanation for male
dominance in typhoid ileal perforation.
Clin Exp Gastroenterol. 2012;5:213-7.
13. Iftikhar A, Bari A, Jabeen U, Bano I.
Spectrum of complications in childhood
Enteric Fever as reported in a Tertiary
Care Hospital. Pak J Med Sci.
2018;34(5):1115-1119.
14. Akullian A, Ng'eno E, Matheson AI, et al.
Environmental Transmission of Typhoid
Fever in an Urban Slum. PLoS Negl Trop
Dis. 2015;9(12):e0004212. Published 2015
Dec 3.
15. Comeau JL, Tran TH, Moore DL, Phi CM,
Quach C. Salmonella enterica serotype
Typhi infections in a Canadian pediatric
hospital: a retrospective case series. CMAJ
Open. 2013;1(1):E56-61. Published 2013
May 2.
16. Dheer G, Kundra S, Singh T. Clinical and
laboratory profile of enteric feverin
children in northern India. Trop Doct.
2012 Jul;42(3):154-6.
17. Mweu E, English M. Typhoid fever in
children in Africa. Trop Med Int Health.
2008;13(4):532-40.
18. Khosla SN, Anand A, Singh U, Khosla A.
Haematological profile in typhoidfever.
Trop Doct. 1995 Oct;25(4):156-8.
19. Gidvani CH, Chandar V, Raghunath D,
Puri RD, Wilson CG, Nagendra A. Enteric
fever - culture and sensitivity pattern and
treatment outcome. Med J Armed Forces
India. 2017;51(2):83-86.
20. Chiu CH, Tsai JR, Ou JT, Lin TY.
Typhoid fever in children: a fourteen-
yearexperience. Acta Paediatr Taiwan.
2000 Jan-Feb;41(1):28-32.