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Department of Medical Microbiology and Immunology, Institute of Biomedical Science, College of Health Sciences, Mekelle University, Ethiopia
Department of Internal Medicine, School of Medicine, Mekelle University, College of Health Sciences, Mekelle, Ethiopia
c
Department of Pediatric medicine, School of Medicine, Mekelle University, College of Health Sciences, Mekelle, Ethiopia
d
Department of Biology, College Natural and Computational Sciences, Mekelle University, Mekelle, Ethiopia
b
A R T I C L E I N F O
Article history:
Received 10 February 2015
Received in revised form 1 April 2015
Accepted 22 April 2015
Keywords:
Diagnosis
Treatment
Febrile-patients
Typhoid
Widal test
Sensitivity
Specicity
Resistance
A B S T R A C T
Objective: To determine diagnostic value of the Widal test, treatment pattern of febrile patients and
antimicrobial drug susceptibility pattern of blood isolates.
Methods: Using cross sectional methods, blood samples were collected for culture and Widal test from
502 febrile outpatients attending Mekelle hospital and Mekelle health center with similar symptoms to
typhoid. Sensitivity, specicity for anti-TH and anti-TO titers using culture conrmed typhoid fever
cases, and Kappa agreement between Titer and slide Widal tests were calculated. Treatment pattern of
patients and antimicrobial susceptibility pattern of the blood isolates was assessed.
Results: From the 502 febrile patients, 8(1.6%) of them had culture-proven typhoid fever. However,
patients who have results indicative of recent infection by O and H antigens of the Widal slide
agglutination test were 343 (68.5%), with specicity and sensitivity of 33% and 100%, respectively. Over
prescription of antibiotics was seen by Widal slide test for Ciprooxacin 268 (76.1%), AmoxicillinClavulanic acid 9(2.6%), Amoxicillin 8(2.4%) and Chloranphenicol 8(2.4%). Tube titer positivity was seen
in 23(5.3%) patients with 75% sensitivity and 95.8% specicity. Widal slide and Tube titer tests showed
poor agreement for both antigens (kappa=0.02 for O) and (Kappa=0.09 for H). A single anti-TH titer of
1:160 and anti-TO titer 1:80 higher in our study showed an indication for typhoid fever infection. Drug
resistance pattern of blood isolates ranges from 0-89.7% for gram positive and 0-100% for Gram negative,
with an overall multi-drug resistance rate of 61.7%.
Conclusion: Patients were wrongly diagnosed and treated for typhoid fever by Widal test. The tube
titration method was relatively good but still had poor sensitivity. Blood isolates showed multi drug
resistance, which may be due to the indiscriminate prescription as seen in this study. Based on our
results, the slide Widal test is not helpful in the diagnosis of typhoid, hence other tests with rapid,
feasible, better sensitivity and specicity are urgently needed in Ethiopia.
2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).
1. Introduction
Typhoid (enteric) fever is an important health problem.1
Reports by the World Health Organization revealed that about
21 million cases and >600,000 annual deaths from typhoid fever
http://dx.doi.org/10.1016/j.ijid.2015.04.014
1201-9712/ 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
97
98
Table 1
Qualitative Slide agglutination results of Widal test among febrile patients
suspected of typhoid fever in Mekelle hospital and Mekelle heath center, MayDecember, 2014.
Widal slide agglutination results
Frequency
Percent
343
34
8
126
502
68.3
6.8
1.6
25.1
100
Fig. 1. Coparsion between blood culture and Widal slide test for typhoide diagnosis.
99
Table 2
Frequency of distribution of semi quantitative tube agglutination test in febrile patients suspected of typhoid fever, May-December, 2014.
Titer
O Antigen
H-Antigen
No agglutination
Frequency
% (n=377)
% (n=502)
Frequency
% (n=351)
% (n=502)
1:20
1:40
1:80
1:160
1:320
1:640
Total
137
144
63
12
15
0
0
377
36.3
38.2
16.7
3.2
4
0
0
100
27.3
28.7
12.6
2.4
3
0
0
74
99
129
91
17
8
5
2
351
23.7
36.8
25.9
3.5
2.3
1.4
0.7
100
19.3
25.7
18.2
3.4
1.7
1.2
0.4
69.9
Table 3
The sensitivity, specicity, PPV, and NPV of titers of anti TO (1:80) and anti TH
(1:160) Widal tests for diagnosis of typhoid among febrile patients in Mekelle
hospital and Mekelle heath center, 2014
Measurement
O-Antigen (%)
H -Antigen (%)
Sensitivity
Specicity
PPV
NPV
87.5
96.4
28
97.8
62.5
98
33.3
99.4
75
95.9
22.2
99.6
4. Discussion
100
Table 4
Antimicrobial resistance pattern of bacterial isolates of febrile patients attending Mekelle hospital and Mekelle heath center, May-Dec, 2014, No (%).
Antibiotics
Tested
AMC
CRO
CN
Do
CIP
SXT
F
E
NOR
V
Bacteria isolated
S.aureus
(n=41)
CoNS
(n=39)
S.pyogen
(n=6)
E.coli
(n=12)
Citrobacter spp
(n=6)
S. typhi
(n=8)
Klebsiella spp
(n=3)
Total
(n=115)
7(17.1)
34(82.9)
16(39)
31(75.6)
18(43)
36(87.7)
NA
21(51)
18(43)
14(34)
9(23)
21(53.8)
7(18)
25(64)
10(25.6)
35(89.7)
NA
19(48.7)
14(36)
9(23)
2(33.3)
1(16.7)
0
4(66.7)
1(16.7)
5(89.3)
NA
1(16.7)
1(16.7)
0
3(25)
9(75)
3(25)
6(50)
1(8.3)
10(83)
8(66.7)
NA
5(41.7)
NA
2(33.3)
4(66.6)
2(33.3)
4(50)
3(50)
1(16.7)
5(83.3)
NA
1(16.7)
NA
2(25)
2(25)
3 (37.5)
5(62.5)
1(12.5)
4(50)
6(75)
NA
3(37.5)
NA
2(75)
3(100)
0
3(100)
1(33.3)
3(100)
3(100)
NA
3(100)
NA
27(23.5)
73(63.5)
31(27)
78(67.8)
35(30.4)
94(81.7)
22(19.1)
41(35.7)
45(39.1)
23(20)
CoNS=Coagulase negative Staphylococci, AMC=Amoxicillin-clavunilic acid, CRO=Ceftriazone, CN=Gentamicin, E=Erythromycin DO=Doxycycline, CIP=Ciprooxacin,
SXT=Trimethoprim-sulphamethoxazole, NOR=Noroxacin, F=Nitrofurantonin, V=vancomycin, NA=Not Applicable.
Table 5
Multiple drug resistance patterns of bacterial isolates from blood of febrile patients in Mekelle hospital and Mekelle heath center, May-December, 2014.
Bacterial isolates and their Antibiogram (Resistance pattern) No (%)
R0
R1
R2
R3
R4
R5
R6
R7
R8
R9
S.aureus (n=41)
CoNS
(n=39)
S. pyogen
(n=6)
E.coli
(n=12)
S.typhi
(n=8)
Total
(115)
3(7.3)
7(17.1)
4(9.8)
5 (12.2)
5(12.2)
4(9.8)
6(14.6)
4(9.8)
3(7.3)
____
5(9.1)
4(9.1)
8(20.5)
8(20.5)
5(13.6)
3(6.8)
5(9.1)
5(9.1)
1(2.3)
____
____
1(16.7)
2(33.3)
1(16.7)
1(16.7)
1(16.7)
____
____
____
____
____
4(.3)
2(13.3)
2(20)
3(26.7)
____
1(6.7)
____
____
____
____
1(16.7)
1(16.7)
1(16.7)
2(33.3)
____
____
____
____
____
3(37.8)
1(12.5)
2(25)
1(12.5)
____
1(12.5)
____
____
____
____
1(33.3)
____
2(75)
____
2(75)
1(33.3)
____
____
____
____
12(10.3)
18(15.7)
21(18.3)
18(15.7)
18(15.7)
10(8.7)
12(10.3)
9(7.8)
4(3.5)
____
CoNS - coagulase negative Staphylococci; R0 - sensitive to all antibiotics tested; R1, R2, R3, R4, R5, R6, R7, R8, R9, resistant to one, two, three, four, ve, six, seven, eight, nine
antibiotics, respectively.
and high NPV (99.6%). Similar reports were seen from Egypt (5.7%
of PPV and 98% of NPV)18 and Ethiopia (98.9% NPV and 5.7% NPV).2
Though not as high as the slide Widal test, a signicant number
of patients were still reported falsely as positive (PPV=22.2%) by
Tube titration methods, which could be due to cross reacting
antibodies by infections other than typhoid fever.
In our study positive titer was found in 12 (9%) and 8 (6%)
patients for TO and TH, respectively by other non salmonella
species. This was clearly seen in a study conducted in Cameroon
where out of the total in febrile patients clinically similar to
typhoid, 45% were malaria cases and only 2.5% were true typhoid
cases4, proving that there are febrile infections that induces cross
reacting antibodies with the somatic and agellar antigens. In this
study there were two culture conrmed cases of typhoid but had a
negative titer. Possible reasons for this are early blood collection
time before disease or inadequate bacterial inoculation to induce
antibody production11, and more importantly previous antibiotic
treatment of patients even if no patients told us of taking any
antibiotics during our study.
Slide agglutination and standard tube titration results were
compared and results revealed that there was statistically poor
agreement between both antigens (kappa=0.02 for O) and
(Kappa=0.09 for H), similar to the study conducted in India with
poor agreements between the tests14, but in contrast to this, fair
agreement results were reported from other areas2,19.
The antimicrobial susceptibility pattern of blood isolates was
determined for the commonly available and prescribed antibiotics.
Overall the range of drug resistance pattern for gram positives was
from 0% - 89.7% and from 0% -100% for gram negative bacteria, which
is similar to the result from other part of Ethiopia, which was
101
102
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and Antibody Response with the Duration of Illness in Diagnosis of Typhoid Fever.
Australian Journal of Basic and Applied Sciences 2010;4(4):60914.
18. Mamo Y, Belachew T, Abebe W, Gebre-Selassie S, Jira C. Pattern of Widal
agglutination reaction in apparently healthy population of Jimma town, southwest Ethiopia. Ethiop Med J 2007;45(1):6977.
19. Zenebe T, Kannan S, Yilma D, Beyene G. Invasive Bacterial Pathogens And Their
Antibiotic Susceptibility Patterns In Jimma University Specialized Hospital,
Jimma, Southwest Ethiopia. Ethiop J Health Sci 2011;21:1.
20. Dagnew M, Yismaw G, Gizachew M, Gadisa A, Abebe T, Tadesse T, et al. Bacterial
prole and antimicrobial susceptibility pattern in septicemia suspected
patients attending Gondar University Hospital, Northwest Ethiopia. BMC Research Notes 2013;6:289.
21. Dessalegn L, Shimelis T, Tadesse E, Gebre-selassie S. Aerobic bacterial isolates
from post-surgical wound and their antimicrobial susceptibility pattern: a
hospital-based cross-sectional study. E3 Journal of Medical Research 2014;
3(2):01823.
22. Harbarth S, Ferrie`re K, Hugonnet S, Ricou B, Suter P, Pittet D. Epidemiology and
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Arch Surg 2002;137:13539.