COMPARATIVE STUDY BETWEEN TUBERCULIN SKIN TEST AND
SERUM ALBUMIN LEVEL IN PATIENTS WITH ACTIVE PULMONARY
TUBERCULOSIS
Ahmad Abdelsadek Mohammad MD*.Osama E.Mohammad MD*Abeer A. ShomanMD**
Chest Department - Faculty of medicine Benha University*.Physiology department Faculty of
Medicine Benha University**.
Abstract
Aim of the Work: To study the possible relationship between severity of tuberculin skin test
reaction and serum albumin level in patients with active pulmonary tuberculosis.
Subjects and Methods: 40 patients with active pulmonary tuberculosis just before initiation of
treatment, that were selected from chest outpatient clinic, Benha university hospital, they were
classified into:Group A included twenty patients with serum albumin level below 3.5g/dl. This group
included 17 males (85%) and 3 females (15%) with their ages ranging from 23 to 70 years. And Group
B included twenty patients with serum albumin level ≥ 3.5g/dl. this group included 16 males (80%) and
4 females (20%) with their ages ranging from 15 to 68 years. . The patients were subjected for full
clinical evaluation, History of any other co-morbidity that may affect tuberculin skin test
reactions were excluded like previous anti tuberculosis treatment.HIV infection, alcoholism and
drug abuse, chronic renal failure, neoplasmic diseases and chronic use of corticosteroids. General
&local
examination, laboratory tests including complete blood count (CBC),erythrocyte
sedimentation rate (ESR).liver and kidney function tests, plain chest x-ray (P.A. and lateral
views), Tuberculin skin test using Mantoux technique, Sputum for acid fast bacilli by Z. N. stain
for three consecutive days and Serum albumin level at the same time of Tuberculin test.
Results: According to this study serum albumin level in group A was ranging from 1.5-3.4 gm/dl
with mean 2.6±0.48 and in group B was ranging from 3.5-4.5 with mean 3.85±0.33. These results
showed statistical significant difference between the two groups, In the present study, tuberculin
skin test diameter in (group A) was ranging from 5-15mm with mean 7.5±3.94 and in (group B)
was ranging from 12-30mm with mean 20.9±5.51. Which showed statistically significant
difference between the two groups, in our study there was a statically significant positive
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correlation between intensity of tuberculin skin reaction at 72 hours and serum albumin levels in
both group.
Conclusion:
Patients with active pulmonary tuberculosis and lower serum albumin levels react with weaker
skin responses to tuberculin test.
Key words: active pulmonary tuberculosis, tuberculin skin test, serum albumin levels.
INTRODUCTION
Tuberculosis or TB (short for tubercle bacilli) is a common and often deadly
infectious disease caused by various strains of mycobacteria, usually Mycobacterium
tuberculosis in humans. Tuberculosis usually attacks the lungs but can also affect other parts of
the body [ 1].
Tuberculin skin test (TST) is a useful diagnostic test for evaluating persons who have
symptoms of tuberculosis or who are suspected of being infected with M. tuberculosis [ 2] .
Tuberculin skin test (TST) is the standard test for the diagnosis of asymptomatic
tuberculous infection.Tuberculin a broth culture filtrate of tubercle bacilli was first prepared by
(Robert Koch) in 1891. Subsequently a standardized version of Tuberculin, the purified protein
derivative (PPD) was introduced in 1934 [ 3].
Serum albumin is the most abundant protein in human plasma. Albumin is synthesized in the
liver as preproalbumin. The rate of synthesis is dependent on protein intake, subjected to feed back
regulation by plasma level, oncotic pressure, inflammation and hormones. During times of increased
albumin loss, the liver can increase the rate of synthesis [ 4].
Hypoalbuminemia is a common problem among persons with acute and chronic medical
conditions, malnutrition is observed frequently in patients with pulmonary tuberculosis due to
anorexia [ 5].
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AIM OF THE WORK
To study the possible relationship between severity of tuberculin skin test reaction
and serum albumin level in patients with active pulmonary tuberculosis.
PATIENTS AND METHODS
The study included 40 patients with active pulmonary tuberculosis just before initiation
of treatment, that were selected from chest outpatient clinic , Benha university hospital, in the
period from march 2010 to December 2011, they were classified into:
Group A: included twenty patients with serum albumin level below 3.5g/dl. This group included 17
males (85%) and 3 females (15%) their ages ranging from 23 to 70 years.
Group B: included twenty patients with serum albumin level ≥ 3.5g/dl. This group included 16 males
(80%) and 4 females (20%) with their ages ranging from 15 to 68 years.
Inclusion criteria
Patients suffering from active pulmonary tuberculosis (smear positive) defined as one or
more initial sputum smear examinations positive for Acid Fast Bacilli by microscopy [ 6].
Exclusion criteria
● Previous anti tuberculosis treatment.
● HIV infection.
● Alcoholism and drug abuse.
● Chronic renal failure.
● Neoplasmic diseases
●Chronic use of corticosteroids
All patients were subjected to:
(1) Full History tacking and physical examination.
With special attention to fever, cough, loss of weight and appetite, night sweats, weakness
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and malaise.Physical signs, such as pallor and weight loss, rales, bronchial breathing.
(2) Laboratory tests.



Complete blood count (CBC).
Erythrocyte sedimentation rate (ESR).
Liver and Kidney function tests.
(3) Plain Chest X-ray P-A view
Chest x ray was done to detect radiological classification according to the extent and
exclude an associated lung disease.
(4) Tuberculin skin testing by (Mantoux technique).
By using 0.1ml (5 tuberculin units) of PPD RT tween 80 administrated intradermally in
the volar surface of the forearm. then reading after 48-72 hours, a positive reaction is indicated
by induration of > 10 mm in size.
(5) Sputum for acid fast bacilli by Z. N. stain.
Collection of sputum: Three first morning sputum specimens obtained after a deep
productive cough for three consecutive days, ask the patients to cough into a sterile screw cap
cups, 5-10 ml of sample of each time is appropriate [ 7].The specimens were kept at 4cº prior to
processing with N-Acetyl-L-Cysteine- NaOH (NALC-NaOH), for liquefaction, decontamination
and concentration [ 8].
(6) Serum albumin level at the same time of Tuberculin test.
Statistical analysis
The program used was SPSS version 16. Quantitative data were analyzed using mean and
standard deviation, while frequency and percentage were used with qualitative data. Student t
test was used to compare means of different groups, while chi square and z test to compare
frequencies. Pearson correlation was used to find relationships.
Statistical significance was set at p < 0.05 [ 9].
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RESULTS
Table (1): Age distribution among the studied groups.
Variable
Groups
Range
Mean
±SD
Group A
23-70
44.25
15.55
Group B
15-68
35.3
14.77
Student
t test
P value
1.87
0.07 NS
Age
Table (2): Sex distribution among the studied groups.
Group A
Group B
Total
Sex
No
%
No
%
No
%
Male
17
85.0
16
80.0
33
82.5
Female
3
15.0
4
20.0
7
17.5
Total
20
100.0
2
100.0
40
100.0
S = significant
FET
P value
0.173
1.0 ( N.S.)
N.S = non significant
Table (3): Radiological classification according to the extent among groups.
Group A
Group B
Total
X ray finding
Minimal
Moderate
advanced
Far advanced
No
%
No
%
No
%
10
45.0
8
40.0
17
42.5
7
35.0
8
40.0
15
37.5
3
15.0
4
20.0
7
17.5
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FET
P
value
0.243
0.89
)N.S)
Total
20
100.0
20
100.0
40
100.0
Table (4):Serum albumin levels among studied groups.
Variable
Groups
Range
Mean±
SD
Group A
1.5-3.4
2.6±
0.48
Group B
3.5- 4.5
3.85±
0.33
Albumin
Student
t test
P value
9.51
0.001 (S)
This table shows that there is statistically significant difference between group A and group B as
regarding serum albumin (p=0.001).
Table (5): The diameter of induration in the tuberculin skin test of the studied
groups
after 72 hours.
Variable
Groups
Range
Mean±
SD
Tuberculin
test
Group A
5-15
7.5±
3.94
Group B
12-30
20.9±
Student t
test
P value
8.84
0.001 (S)
5.51
This table shows that there is a significant tendency for the 72 hours reaction to be larger among
group B (p=0.001).
Figure (1): Correlation between intensity of tuberculin skin
reaction after72 hours and serum albumin levels in group A.
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16
y = 7.8924x - 13.02
R² = 0.9417
Tuberculin test diameter
14
12
10
8
6
4
2
0
-2
0
0.5
1
1.5
2
Albumin
2.5
3
3.5
4
This figure shows positive statistical significant correlation between intensity of tuberculin skin
reaction after 72 hours and serum albumin levels in group A
Figure (2): Correlation between intensity of tuberculin skin
reaction after 72 hours and serum albumin levels in group B.
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35
y = 15.804x - 39.866
R² = 0.8859
Tuberculin test diameter
30
25
20
15
10
5
0
0
1
2
3
4
5
Albumin level
This figure shows positive statistical significant correlation between intensity of tuberculin skin
reaction after 72 hours and serum albumin levels in group B.
DISCUSSION
Tuberculin skin test is a useful diagnostic test for evaluating persons who have symptoms
of tuberculosis or who are suspected of being infected. Positive tuberculin skin test only
indicates infection and by itself is not diagnostic of TB disease as it fails to distinguish between
active disease and prior sensitization by contact with M.tuberculosis [10].Malnutrition and
tuberculosis are both problems of considerable magnitude, these two problems tend to interact with
each other and link between them has long been recognized. Malnutrition can lead to secondary
immunodeficiency that increase the host’s susceptibility to the development of clinical disease. In
patients with tuberculosis, it leads to reduction in appetite, nutrition malabsorption and altered
metabolism [11]. In the present study 40 patients with active pulmonary tuberculosis was divided
into group A with serum albumin level below 3.5g/dl and their ages ranging from 23 to 70 years
and mean was 44.25±15.55 and group B with serum albumin level ≥ 3.5g/dl and their ages
ranging from 15 to 68 years and mean was 35.3±14.77, these results showed no statistical
significant difference between the two groups as regarding age distribution (Table 1).
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The current study group A included 17 males (85%) and 3 females (15%) and group B
included 16 males (80%) and 4 females (20%) which revealed
no statistical significant
difference (Table 2).The radiological classification of the extent of the disease in current study
was; (group A) minimal disease: 10 patients (45%), moderate advanced disease: 7 patients (35%)
and far advanced disease: 3 patients (15%) and in patients (group B), minimal:8
patients(40%),moderate advanced:8 patients(40%), far advanced: 4 patients(20%) The results
revealed no statistical significant difference between two groups (Table 3).
According to this study serum albumin level in group A was ranging from 1.5-3.4
gm/dl with mean 2.6±0.48 and in group B was ranging from 3.5-4.5 with mean 3.85±0.33. These
results showed statistical significant difference between the two groups (Table 4). This result was
in accordance with those of Stylianos et al., [12] ,their study included 48 patients with active
pulmonary tuberculosis was divided into group A with low serum albumin and their mean serum
albumin level was 2.95±0.91 and group B with normal serum albumin level and their mean
serum albumin level was 3.92±0.6. TB can cause diverse laboratory abnormalities such as
anemia, increased erythrocyte sedimentation rate and low serum albumin. Malnutrition per se
had a more pronounced effect on serum albumin concentration in TB patients. Thus, all chronic
infections such as TB can cause decrease production of serum albumin [13].In the present study,
tuberculin skin test diameter in (group A) was ranging from 5-15mm with mean 7.5±3.94 and in
(group B) was ranging from 12-30mm with mean 20.9±5.51. which showed statistically
significant difference between the two groups (Table 5).This result was in agreement with those
of Stylianoset al., [12] ,their study included group A with low serum albumin and their mean
tuberculin skin test diameter was 11.3±2.1 and group B with normal serum albumin and their
mean tuberculin skin test diameter was 18.4±3.9, the study showed statistically significant
difference between the two groups . In our study there was a statically significant positive
correlation between intensity of tuberculin skin reaction at 72 hours and serum albumin levels in
both groups (Figure 1, 2).This result was in accordance with Kardjito and Donosepoetro, [14]
who studied the mantoux test in tuberculosis, the result showed a statistically significant positive
correlation between intensity of tuberculin skin reaction and serum albumin levels.
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Also this result was in accordance with Michaelides et al., [15] who studied relationship
between tuberculin hypersensitivity and serum albumin level in patients with pulmonary
tuberculosis, their study included 42 patients (35 males and 7 females) aged 33.04±15.7. The
diameter of induration was 17.8mm±6.01 and serum albumin levels were 7.27g/dl±0.86.Analysis
showed a statistically significant positive correlation between intensity of tuberculin skin
reaction and serum albumin levels. These findings indicated that tuberculous patients with lower
albumin levels seem to react with weaker skin responses to tuberculin compared to those with
rather normal albumin levels which could be explained by, malnutrition that cause suppression of
delayed hypersensitivity reaction; false negative tuberculin reactions are very frequent in
advanced malnutrition, malnutrition has been linked with decreased immune function[16].
CONCLUSIONS
-
Tuberculous patients with lower serum albumin levels react with weaker skin responses to
tuberculin. As there was a significant positive correlation between intensity of tuberculin
skin reaction at 72 hours and serum albumin levels
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