Egyptian Journal of Chest Diseases and Tuberculosis (2016) 65, 629–635

HOS
TED B Y The Egyptian Society of Chest Diseases and Tuberculosis
Egyptian Journal of Chest Diseases and Tuberculosis
www.elsevier.com/lo
cate/ejcdt
www.sciencedirect.c
om

ORIGINAL ARTICLE
The role of supplementary vitamin D in treatment course of pulmonary
tuberculosis

a a a,
Essam Gouda Hassanein , Enas Elsayed Mohamed , Ayman Ibrahim Baess *, Eman
b c
Tayae EL-Sayed , Ahmad Madi Yossef

a Department of Chest Diseases, Alexandria Faculty of Medicine, Egypt

b Department of Clinical and Chemical Pathology, Alexandria Faculty of Medicine, Egypt
c EL-Maamoura Chest Hospital, Alexandria Governorate, Egypt

Received 10 March 2016; accepted 16 March 2016

Available online 4 April 2016

KEYWORDS Abstract Background: Vitamin D insufficiency/deficiency is

Vitamin D; associated with impaired immune function and increased risk of
Pulmonary active pulmonary tuberculosis (TB).
tuberculosis Objectives: To evaluate the role of vitamin D as supplementary
treatment with the first line anti- tuberculous drugs (rifampicin,
izoniazide, ethambutol and pyrazinamide) in treatment course of
patients with active pulmonary tuberculosis.
Methods: We conducted a case-control study in El Maamora chest
hospital, Alexandria gover- norate, Egypt, including 60 adult patients
with active pulmonary TB of 30 patients each. Patients in group I
(cases) received vitamin D (200,000 IU) intramuscular injection
once besides anti- tuberculous drugs, while patients in group II
(controls) were randomly selected from the hospital registry who
received the first line anti-tuberculous treatment only. The primary
outcome was eval- uation of conversion time of sputum smear. The
secondary outcome was clinical improvement as assessed by TB score.
Measurements and main results: Mean ± SD age of all patients
was 41.55 ± 14.91 years. The study included 44 (73.3%) males and
16 (26.7%) females. Vitamin D deficiency/insufficiency was detected
in 54 (90%) patients. Comparing the two groups, there was a rapid
decline in sputum conver- sion time and severity classes of TB score in
group I compared to group II (p < 0.001 and p = 0.02,
respectively). No accelerates the improvement observed in vitamin D supplemented TB
complications ther- apy. Vitamin D is safe when added to anti-tuberculous drugs.
secondary to Vitamin D deficiency/insufficiency is common among TB patients.
supplementary Further studies are required to validate this observation and define a
vitamin D were cut off of vitamin D level to prevent immunological alterations.
met all through 2016 The Egyptian Society of Chest Diseases and Tuberculosis.
the study. Production and hosting by Elsevier B.V. This is an open access article
Conclusion: under the CC BY-NC-ND license
Vitamin D (http://creativecommons.org/licenses/by-nc- nd/4.0/).

* Corresponding author at: Chest Department, Secretary Office, Alexandria Faculty of Medicine,
Champillion St, Alexandria, ElAzareita 21131, Egypt. Tel.: +20 1006822068.
E-mail address: ayman.baeis@yahoo.com (A.I. Baess).
Peer review under responsibility of The Egyptian Society of Chest Diseases and Tuberculosis.
http://dx.doi.org/10.1016/j.ejcdt.2016.03.004
0422-7638 2016 The Egyptian Society of Chest Diseases and Tuberculosis.
Production and hosting by Elsevier B.V. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
118 E.G. Hassanein et al.
Vitamin D in treatment course of pulmonary tuberculosis 119

I [2]. This metabolite Lower vitamin D

n modulates the host level was reported to t
t response to be associated with a i
r Mycobacterial higher risk of m
o infection by developing active e
d induction of reactive pulmonary
u tuberculosis [14]. The El-Maamoura chest
nitrogen and oxygen
c role of vitamin D in hospital in
inter- mediate, [5,6]
t modifying the Alexandria
suppression of
i treatment course of governorate, Egypt,
matrix
o pulmonary from January to
metalloproteinase
n tuberculosis is still a August 2015.
enzymes implicated
in the pathogenesis matter of debate
Tuberculosis (TB) S
of pulmonary cavita- [15,16]. We aimed t
is a chronic this work to evaluate
tion [7] and u
specific bacterial the role of vitamin D
induction of anti d
infection caused by as supple- mentary
microbial peptide y
bacteria of the treatment when
catheliciden [8,9]
Mycobacterium added to the first
which induces d
tuberculosis [1]. line anti-
autophagy [10]. e
Human monocytes tuberculous drugs, s
The human
have receptors for (rifampicin, i
vitamin D receptors
1,25 izoniazide, g
(VDRs) are
dihydroxyvitamin D ethambutol, and n
polymorphic.
that activates anti pyrazinamide) in the
Carriage of the t
mycobacterial treatment course of We conducted a
allele of taq I VDR
responses in human patients with active randomized, case
polymorphism is
mono- cytes and pulmonary control clinical trial,
associ- ated with an
macrophages by tuberculosis. includ- ing adult
increase in calcitriol-
enhancing (P18 years old)
induced phagocytosis
phagocytosis and M patients who had
of M. tuberculosis in
granu- loma e active pulmonary TB
vitro [11] and more
formation [2]. t diagnosed by sputum
rapid sputum h
Vitamin D is examination (smear
conversion in patients o
synthesized in the microscopy or
with pulmonary d
skin during exposure mycobacterial culture)
tuberculosis [12]. s
to ultra violet B or by World Health
While, carriage of f
(UV-B) radiation and Organization clinical
allele of the fok I S
is also present in criteria [17].
VDR polymorphism t
foods. Vitamin D is Exclusion criteria
is associated with a u
readily metabolized were corticosteroids
reduction in d
in the liver, to form or immuno-
transcriptional y
25 hydroxy-vitamin suppressive
activity, [13]
D [25(OH)D], the s treatment, human
reduction of
accepted measure of i immunodeficiency
calcitriol-induced
vita- min D status t virus (HIV), multi-
phagocytosis, and
[3,4]. Calcitriol, the e drug resistant TB
slower sputum smear
active metabolite of (MDR-TB), Liver
or culture conversion
vitamin D, induces a cirrhosis, renal fail-
in pulmonary
anti mycobacterial n ure, vitamin D
tuberculosis [11].
activity in vitro d
120 E.G. Hassanein et al.
supplementation, (cases) included e measured at the
malignancies, patients who r midpoint between
hypercalcemia. received both the s the acromion and
first line anti e olecranon over the
P biceps of the non
tuberculous
a e dominant arm, using
treatment besides
t f a non stretchable
i supplementary
f measuring tape.
e vitamin D [200,000
e Severity of TB
n IU of vitamin D
c disease was assessed
t (25(OH)vitamin D) t by the TB score [20].
s intramuscular s
injection once, TB score has been
(Devarol-S-ampoule, validated in
This study enrolled We questioned the
Memphis for another cohort and
sixty patients with patients for the
pharmaceu- ticals & has been grouped in
active pulmonary following adverse
chemicals industries, severity classes as fol-
tuber- culosis divided effects related to
El-Amirya, Cairo, lows: I (0–5 points),
into two groups of hypercalcemia e.g.
Egypt). Group II II (6 or 7 points), or
thirty patients each. nausea, vomiting,
(controls) included III (8 points or
Group I excessive thirst,
patients who were more).
anorexia, symptoms Serum level of 25-
randomly selected of kidney stones, and hydroxyvitamin D
from the hospital confusion. [21] was measured
registry who received at
the first line anti time of diagnosis and
M after 2 months of
tuber- culous e
treatment only. anti-tuberculous
a
ther- apy with
s
F chemiluminescence
u
o immunoassay
r
l e technology using
l m ADVIA Centaur
o e immunoassay system
w n (Siemens Healthcare
- t Diagnostics, 1717
u s Deerfield Road,
p Deerfield, IL 60015-
Body mass index 0778, USA). Serum
Patients were (BMI) was assessed vitamin D was
followed up weekly using the following defined as deficient
by microscopic for- mula: BMI = (<20 ng/ ml),
examination of insufficient (20–30
weight/(height)2.
sputum for acid ng/ml), sufficient
Height was
fast bacilli of measured by a (30–100 ng/ml), or
pulmonary meter scale; weight toxic (>100 ng/ml).
tuberculosis, [18,19] was measured in Serum levels of
and calculation of kilograms, using the Calcium as well as
TB score [20]. same weight scale at albumin, both were
each patient visit. mea- sured at time of
A Mid–upper arm inclusion and at the
d circumfer- ence was end of 2nd month.
v Serum albumin was
Vitamin D in treatment course of pulmonary tuberculosis 121
measured in order to lung auscultation
correct serum finding, fever, low
calcium using the body mass index,
following equation: and low mid–upper
Corrected calcium arm
(mg/dL) = serum
calcium + 0.8 (4
serum albumin
(g/dL)) [22]
Hypocalcemia,
normo-calcemia or
hypercalcemia were
defined when
corrected serum
calcium levels were
below 8.5 mg/dl, 8.5–
10.10 mg/dl or
exceeding 10.10
mg/dl, respectively
[22].

O
u
t
c
o
m
e

The primary
outcome was
evaluation of
conversion time of
sputum smear. The
secondary outcome
was clinical improve-
ment as assessed by
TB score [20]. The
TB score is a newly
developed tool
aimed at assessment
of change in the
clinical state in
patients with TB. It is
based on points
assigned to signs and
symptoms, including
cough, hemoptysis,
dyspnea, chest pain,
night sweating,
anemia, tachycardia,
122 E.G. Hassanein et al.
Vitamin D in treatment course of pulmonary tuberculosis 123

circumference, giving stan- dard deviation using Mann Whitney Group I included 11
patients a TB score and median. test. To compare (36.7%) non-
from 0 to 13. Change Comparison between between the different smokers and 19
in TB score has been different groups periods, Wilcoxon (63.35%) smokers.
shown to detect regarding categorical signed rank test was Group II included 8
clinical change as variables was tested applied. Correlations (26.7%) non-
well; a high TB score using Chi- square between two smokers and 22
correlates well with test. When more quantitative variables (73.3%) smokers.
mortality and low TB than 20% of the were assessed using There was no
scores correlate with cells have expected spearman coefficients statistically
favorable outcomes, count less than 5, regarding normality significant differ-
cure, and completed correction for chi- of the data. ence between the
treat- ment [20]. square was Significance of the two groups
conducted using obtained results was regarding smoking
S Fisher’s Exact test judged at the 5% status (p = 0.405).
t or Monte Carlo level. In group I, on
a correction. McNe- commencing the
t mar–Bowker and R anti-TB treatment,
i Marginal e Serum vitamin D
s s deficiency was
homogeneity test
t u defined in 29(96.6%)
was applied for
i l
ordinal data .The patients, serum
c t
distributions of vitamin D
a s
quantitative variables insufficiency was
l
were tested for detected in a single
normality using Group I included 22 (3.4%) patient while
a (73.3%) males and 8
n Kolmogorov– there was no cases
Smirnov test, Sha- (26.7) females. Sex- where vitamin D
a
piro–Wilk test and matched controls sufficiency or serum
l
D’Agstino test, If it were selected from vitamin D toxicity
y
s reveals normal data the hospital registry was found. Mean
i distribution, where 22 males and serum vitamin D
s parametric tests was 8 females were level at the start of
applied. If the data included in group II. treatment was 9.83
Data were fed to the were abnormally In group I, mean ± 5.88 ng/dl. At the
computer and distributed, non- ± SD age was end of 2nd month,
analyzed using IBM parametric tests 41.70 ± 14.87 years. serum vitamin D
SPSS were used for Age- matched deficiency was
software package normally distributed controls were detected in 7 (23.3%)
(IBM SPSS Statistics data, comparison selected as group II patients, serum
for Windows, between the two from the registry vitamin D
Version with a mean ± SD insufficiency was
studied groups were
20.0., IBM Corp., age of 41.40 ± traced in 17 (56.7%)
done using
Armonk, NY) 14.94 years. There patients, serum
independent t-test,
Qualitative data was no statistically vitamin D
also paired t-test is
were described using significant difference sufficiency was found
used to analyze two
number and percent. between the two in 6 (20%) patients,
paired data. For
Quantitative data studied groups while there were no
abnormally dis-
were described using regarding age (p = detected patients
tributed data,
range (minimum and 0.938). Regarding with serum vitamin
comparison was done
maximum) mean, smoking status,
 124 E.G. Hassanein et al.
D toxicity. Mean Notably, there was a anti-TB treatment who were severity
serum vitamin D statistically (p < 0.001) Fig. 2. class (SC II) and
level at the end of significant difference Group I included 16 patients (53.3%)
second month of between the cases at 17 patients (56.7%) who were (SC III),
treatment was 23.76 the start of treatment who were sputum Mean TB score was
± 7.09 ng/dl. and the end of 2nd smear negative for 2.53 ± 0.51. Group
month of anti-TB acid fast bacilli at II included 13
treatment regarding 3rd week, 9 patients patients (about 43.3
levels of serum (30%) who were %) who were (SC II)
vitamin D (p < sputum smear and 17 patients
0.001) Fig. 1. negative at 4th week (about 56.7 %) who
At the start of and 4 patients (13.3 were (SCIII), Mean
anti-TB treatment, %) who were TB score was 2.57 ±
group I included 22 sputum smear 0.50. There was no
patients (about negative at 5th statis- tical
73.3%) who were week. Mean significant difference
hypocalcemic, 8 conversion time ± between the two
patients (26.7%) who SD = 3.57 ± 0.73 groups regarding TB
were normo-calcemic, weeks. While group score at the start of
and there were no II included 3 patients treatment with anti
patients with (10%) who were tuberculous drugs (p
hypercalcemia. The sputum smear = 0.795) Fig. 5.
mean corrected serum negative for acid At the time of
calcium level at the fast bacilli at 5th conversion of sputum
start of treatment week, 8 patients smear or end of 2nd
was 8.19 ± 0.71 (26.7 %)who were month, group I
mg/dl. At the end sputum smear included 26 (86.7%)
of negative at 6th patients who were
2nd month of anti- week, 5 patients severity class (SC I)
TB treatment, (16.7%) who were and 4 (13.3%)
detected 4 patients sputum smear patients who were
(about negative at 7th week (SC II). Mean TB
13.3%) who were and 14 patients (46.7
hypocalcemic, 15 %) who were sputum
patients (50%) who smear negative at
were normo-calcemic, 8th week. Mean
11 patients conversion time ±
(36.7%)who were SD = 7.0 ± 1.08
hypercalcemic. The weeks. There was a
mean corrected statistical significant
serum calcium level difference between
at the 2nd month of the two groups
anti-TB treatment regarding the time of
was 3.15 ± 0.55 sputum conversion
mg/dl. There was a (p < 0.001) Figs. 3
statisti- cal significant and 4. Figure 1 Serum
difference in serum At the start of anti- vitamin D
calcium level at the TB treatment for measurement in
start and after 2- patients in group I, patients in group I at
months of initiating 14 patients (46.7%) base line and 2
 Vitamin D in treatment course of pulmonary tuberculosis 125
months after
initiation of
supplemented
treatment.
126 E.G. Hassanein et al.
Vitamin D in treatment course of pulmonary tuberculosis
Figure 2 Corrected serum calcium level in
patients in group I at baseline and 2 months
after initiation of supplemented therapy.
score was 1.13 ± 0.35. Group II included 18
(60%) patients who were severity class (SC I)
and 12 (40%) patients who were (SC II), Mean
TB score was1.40 ± 0.50. There was a
statistical significant difference between the
two groups regarding TB score at the time
of conversion of sputum smear or end of
2nd month (p 0.020)
Fig. 6.
Discussi
on
Vitamin D insufficiency/deficiency is associated
with impaired immune function and
increased risk of active TB. It has recently
been proposed that vitamin D accelerates
resolution of host inflammatory responses
and this may contribute to the improvement
observed in vitamin D supplemented TB
therapy [23].
In the present study, the mean age was 41.70
± 14.87 years in patients in group I while it
was 41.40 ± 14.94 years in the control group
(II).Similarly, in El Maamora chest hospital,
Mohamed et al. [24] studied the clinical
presentation, compli- cation and outcome of
patients suffering from multi-drug resis- tant
tuberculosis (MDR-TB) and extensively drug
resistant
127
(XDR-TB) and found that the mean
age was 40.36
± 14.74 years. Similarly, Sayed et al. [25]
studied the role of interferon gamma release
assays (IGRAs) in the diagnosis of pulmonary
TB and found the mean of age was
38.75
± 10.45
years.
This may be explained by fact that TB is a
disease of young and middle-aged adults with
most cases occurring between the ages of 20 to
40 years due to increase of exposure to
infection in this active age group and the effect
of physical and mental stress [26].
The present study revealed that the
majority of patients were males (73.3%) in
both groups. Similarly, Mohammed et al.
[24] reported males were 70% of patients,
Elrefaey et al. [27] reported that males were
79.3% of cases.
This coincides with the epidemiological
picture of tubercu- losis where males are more
exposed to infection in the commu- nity than
females. Male and female rates of infection are
nearly the same from childhood through young
adult life. Thereafter, the rate of infection in
males becomes increasingly greater than in
females in the absence of widespread HIV
infection. Also in some instances, women may
have poorer access to the diagnos- tic facilities
[26,28].
Of note, the same or near-same age and
gender in both groups is due to the fact that
after enrollment of all patients in group I,
Age and sex-matched controls were chosen
from the hospital registry.
In the current study, the percentage of
smokers was (63.35%) in group (I) and
(73.3%) in group (II). The role of active
smoking in development of TB is well
known as described by WHO reports from
different countries [29].
Similarly, Ozturk et al. [30] who studied the
effect of smok- ing and indoor air pollution on
the risk of tuberculosis found that patients
who smoke had a fivefold (p < 0.0001)
higher odds of having active tuberculosis
compared with patients who do not smoke.
Also Mohammed et al. [24] found that
128 E.G. Hassanein et al.
50% of MDR patients were tobacco Tobacco smoking increases risk of M.
smokers and 46.8% of tuberculous non- tuberculosis infection by several means namely;
MDR patients were smokers. alteration of muco-ciliary clearance,

30
Cases Control
25
Number of cases

20
17

15 14
10 8
9

5 4 5
3
0 0 0 0 0 0 0
0
1st week 2nd week 3rd week 4th week 5th week 6th week 7th week
8th week
Figure 3 Comparison between the two studied groups according to sputum
conversion time.
 reduced alveolar that patients with
macrophage activity; active TB had lower
immune-depression serum vitamin D
of pulmonary levels than controls
lymphocytes, from similar ethnic
reduction of cytotoxic and social
activity of nat- ural backgrounds;
killer cells and moreover, even with
alteration of the comparable dietary
activity of the intake and sun
pulmonary dendritic exposure, they did not
cells [31]. show the expected
Figure 6 In the current seasonal variation
Figure 4 Mean Comparison between study, there was a .Also Nnoaham et
sputum conversion the two studied statistical significant al. [14] reported
time in both studied differ- ence between earlier that 25-
groups according to
groups. serum vitamin D at hydroxyl
TB score at sputum
the start of anti-TB cholecalciferol levels
conversion or at the treat- ment and that were low in patients
end of 2nd month of at the end of 2nd with TB compared
initiating month after with that of the
supplemented initiation of anti-Tb healthy controls.
treatment. treatment (p < Also Arnedo- Pena
0.001) .This signifies et al. [33] reported
the good response of that vitamin D
patients with active deficiency is
pulmonary TB to associated with TB
vitamin D incidence.
supplemen- tation Compared to our
regardless of the results, Wejse et al.
vitamin D state in [34] reported that
serum before initia- vitamin D
Figure 5 tion of vitamin D insufficiency was
Comparison between therapy. Of note, no common among
the two studied single case patients with TB in
groups according to experienced the study area, but
TB score at day manifestations of severe vitamin D
zero. hypercalcemia, 2 deficiency was rare.
months after Vitamin D
initiation of vitamin deficiency or
D therapy, although insufficiency in our
the presence of patients is not fully
elevated serum explained. This may
calcium level was be attributed to low
seen in 11 (36.7 %) vitamin D intake
patients. and lack of sun
In accordance exposure as most of
with our finding, our patients are of
Sita-Lumsden et al. low socioeconomic
[32] had reported class.
 In the present pulmonary genotype
study, we observed tuberculosis,
that, there was a reported that in
signifi- cant decrease subjects receiving
in sputum conversion 60,000 IU
time in group I cholecalciferol per
(cases) compared to week along with
group II (control) anti-TB treatment,
(p < 0.001). Sputa dura- tion of sputum
of most patients conversion to 100%
(56.7%) in group I negative for AFB
were converted at was
the 3rd week of 6 weeks compared to
initiation of anti-TB 8 weeks in subjects
drugs while in group not receiving chole-
II, sputa of most calciferol. Also,
patients (46.7%) Nursyam et al. [37]
were converted at the reported that
8th week after the pulmonary TB
start of anti-TB patients given
therapy. 420,000 IU of
Our later finding is vitamin D over 6
supported by many weeks had
studies in the liter- significantly higher
ature. Sato et al. [35] sputum conversion
reported that in cured rates as compared to
patients, serum 25 placebo (p 0.002).
hydroxy-vitamin D Compared to our
levels showed a finding, Martineau
significantly negative et al. [38] demon-
cor- relation with strated that
duration until sputum administration of
conversion. This four doses of 2.5 mg
relation- ship vitamin D (100,000
suggests that a low IU, 1 mg = 40,000
serum vitamin D IU) did not affect
level may not only be time to spu- tum
a risk factor for the culture conversion in
development of the whole study
active TB but it may group. However,
also be related to improvement of the
poor treatment serum vitamin D
outcomes in active level was
TB patients. experienced both
Furthermore, Kota safely and quickly
et al. [36] who studied and a faster
the effect of vitamin conversion to
D supplementation negative sputum for
in type 2 diabetes AFB was encountered
patients with in patients with tt
of the Taq I vitamin antimicrobial treat- patients from than that found in
D receptor ment. Such a decline initiation to end of blood donors (2
polymorphism might have resulted treatment, and (IQR 1–4) vs 0 (IQR
suggesting that this from a reduction in declined with a 0–1), p < 0.0001).
subgroup of patients granulomatous similar pattern in Patients who died
with TB might derive burden in patients HIV-infected and had a signifi- cantly
clinical benefit from responding to HIV-uninfected higher TB score at
vitamin D treatment, leading to patients, as well as week 0, week 2, and
supplementation. a decrease in extra- in smear negative week 8 than
Unfortunately and renal 1-alpha and smear positive survivors. Mortality
to the best of the hydroxylation of 25- patients. The risk of was associated with
authors’ knowledge, hydroxy-vitamin D dying during a failure to achieve a
no available data and a fall in serum 1, treatment increased decrease greater
exist regarding the 25- dihydroxyvitamin with higher TB score than 25% in the
genotypes of vitamin D concentrations. at inclusion. For TB score at 2
D receptor TB score assessed patients with a TB weeks. Baseline
polymorphism in at the end of score of >8 at CD4+ cell counts
Egyptian tuberculous treatment also inclusion, mortality (< 200 cells/mm3)
patients. strongly predicted during the 8 months were associated with
In the current subsequent mortality. treatment was 21% mortality but not
study, there was a The TB score is a (45/218) versus 11% with initial TB score
statistical significant simple and low-cost (55/480) for TB score results. They con-
differ- ence between tool for clinical < cluded that the TB
serum calcium at the monitoring of 8 score was increased
start of anti-TB tuberculosis patients during the first
treatment and that in low-resource ( 2 months of
measured at the end settings and may be p treatment among
of 2nd month after used to predict patients who died.
< Failure to achieve a
initiation of anti-TB mortality risk. Low
treatment (p < TB score or fall in TB greater than 25%
0
0.001). Narang et al. score at treatment decrease in TB score
.
[39] reported similar completion may be 0 after 2 weeks of
results. used as a measure of 0 treatment was
Hypercalcemia was improvement [40]. 1 associated with
detected in 19 of 30 In the current ) increased mortality.
patients with smear study, there was a . Repeated clinical
positive pulmonary statistical significant On contrary, scoring during the
tuberculosis taking a differ- ence between Janols et al. [41] intensive phase of TB
daily dose of 10–95 the two groups reported that in TB treatment could be
mg vitamin D. regarding TB score at patients (53.6% of useful to identify
Compared to our the time of sputum whom were HIV co- high-risk patients.
results, Martineau et conversion or at the infected), the median In conclusion,
al. [38] showed that end of the 2nd TB score declined supplementary
serum corrected month after the start from week 0 to week vitamin D when
calcium of anti-tuberculous 2 (8 (IQR 6–9) vs 4 added to first line
concentration treatment (p 0.020). (IQR 2–6)) and anti-tuberculous
declined in both Wejse et al. [34] dropped to a low drugs was of benefit
inter- vention and found that TB score level at week 8, in treatment of
control arms after declined for 96% of which was still active pulmonary
initiation of the surviving signifi- cantly higher TB. This results in
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i 3
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t 1
e proliferation of
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