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El-Adawy et al
________________________________________________________________________________
EVALUATION OF DIFFERENT DIAGNOSTIC MODALITIES OF GENITAL
TUBERCULOSIS AMONG INFERTILE WOMEN
By
Ahmed R. M. EL Adawy*, Mohamed I. Bassiouny** and Wafaa Farghaly***
Departments of *Obstetric Gynacolgy, **Microbiology and ***Pathology
El-Minia Faculty of Medicine
ABSTRACT:
Objective: to estimate the frequancy of genital tuberculosis (T.B) among infertile
women undergoing laparoscopic evaluation in El Minia University Hospital.
- Secondly to assess different diagnostic modalities of genital T.B.
Design: A prospective study.
Setting: Department of Obstetrics & Gynacolgy, Department of Pathology and
Department of Microbiology, Faculty of Medicine, Minia University.
Methods: 150 infertile women undergoing laparoscopy were included into the study
from December 2003 to September 2005, Laparoscope criteria of genital T.B were
observed, any suspicious lesions for T.B. adnexities or peritonitis were biopsied,
peritoneal fluid was obtained for detection of mycobacteria by automated radiometric
BACTEC 460 system and culture in Lowenstein Jensen medium (L.J), lastly Whole
endometrial curettage was taken for histopathology.
Results: The incidence of genital T.B as diagnosed by Laparoscopy was 8% among
study group, the incidence of positive patients was more among rural, low
socioeconomic and low educational level patients. Both laparoscopic findings
confirmed by biopsy and BACTEC showed high sensitivity and specificity (93-95%)
compared to endometrial biopsy (81-83%) and culture in L.J (72-76%) for diagnosis
of genital T.B. Moreover BACTEC showed shorter detection time than L.J.
Conclusion: It is essential for a gynecologist working in developing countries to
anticipate possibility of genital T.B in infertile patients. For the diagnosis of genital
T.B the simultaneous use of BACTEC and L.J is recommended to provide maximal
optimal recovery of isolates from clinical specimens. The time-Saving in BACTEC
provides an excellent facility for gynecologists in patient’s management.
KEY WORDS:
Genital tuberculosis
Infertility
presentation of genital T.B and paucity
of investigations3.
INTRODUCTION:
Tuberculosis (TB) is an
infectious
disease
that
causes
considerable morbidity and mortality.
It is a major socio-economic burden in
developing countries affecting millions
of peoples mostly in the reproductive
age group (15- 45 years)1. It is
involved in about 5-16% of cases of
infertility2. The actual incidence may
be under-reported due to asymptomatic
Tuberculosis is caused by
Mycobacterium tuberculosis. Two
types of TB bacilli are involved. The
bovine bacillus is transmitted through
cattle's milk and the portal of entery is
the intestine. The human type is an air
born infection and the lung is its portal
of entry. TB of the female genital tract
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________________________________________________________________________________
is common among all communities
where pulmonary and other forms of
extra genital TB is prevalent, like in
Egypt.
forthcoming and an evidence of T.B
lesion elsewhere may be lacking. The
abdominal and vaginal examination
may be normal. A high erythrocyte
sedimentation rate is not specific.
Chest X-ray is normal in most cases. A
pelvic
ultrasound
and
hystrosalpingogrphy may be of some help.
Histpathologic
examination
that
reveals typical granuloma or acid-fast
stain and culture of surgical biopsy by
laparoscopy or endometrial biopsy
specimens8.
Genital T.B is commonly
caused by the human subtype of M.
Tuberculosis. After wide use of
specific antituberculosis chemotherapy
there had been a decline in TB
incidence. However there is a
resurgence of TB in recent years which
may be secondary to the pandemic of
H.I.V infection and the associated
compromised immunity, and the
appearance of resistant strains4.
Traditionally the laporatory
diagnosis of TB depends on
demonstration of the causative organism by acid-fast staining and or
growth of the organism on Lowenstien
-Jensen (LJ) medium. Microscopic
examination of acid-fast bacilli needs
at least 10.000 organisms/ml while
culture needs 100 organisms/ ml9.
However organism may need up to 8
weeks to grow in L.J medium. Beside
technical draw backs in demonstrating
M. tuberculosis in the laboratory a
substantial number of TB lesions of the
genital tract are bacteriologically
mute15.
Genital TB occure mostly
secondary to pulmonary TB, comm.only by the haematogenous route in a
manner similar to spread to extrapulmonary sites like urinary tract,
bones and joints etc… The fallopian
tubes are affected in almost 100% of
cases followed by endometrium in
50%,ovaries in 20%, cervix in 5% and
vagina and vulva in <1%5. However
few reports have found endometrium
to be the most commonly involved
site6.
Clinical symptoms are variable,
infertility in 60% of cases but pelvic
pain and menstrual disorder can
occure,
some
patients
remains
asymptomatic. Menstrual irregularities
are due to endometrial caseation,
infertility is due to both endometrial
and tubal pathology and blockage of
ovum
transport.
The
antigonadotrophic effect of Mycobactirum
tuberculosis may be responsible for
menstrual irregularities that occure in
cases of active pulmonary T.B with no
demonstrable lesions in genital tract7.
The BACTEC radiometric
technique has been widely used for
over a decade for the rapid recovery of
mycobacteria from sputum and other
clinical specimens. Several investigators
have
successfully
used
BACTEC 12B medium for isolation of
mycobacteria from blood specimens.
However a large quantity of blood can
not be inoculated into 12B medium
because of resulting turbidity and high
background readings. Another approach is to process the specimen by
lysing the blood cells and then concentrating the specimen by centrifugation.
The introduction of BACTEC 13A
medium eliminates this time-consuming and potentially hazardous step. It
allows a large volume (up to 5 ml) of
The diagnosis of the disease is
difficult. Apart from varied clinical
presentation, a past history of TB or a
history of contact may not be
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El-Adawy et al
________________________________________________________________________________
- BACTEC 13 A Enrichment – to be
added to 13 A medium (0.5 ml/13A
vial).
(B) Principle of the procedure:BACTEC 13 A medium is a modified
7 H 12 medium which support growth
of mycobacteria when supplemented
by 13 A Enrichment. The liberation of
CO2 from (C) lableled substract
present in the medium is monitored,
which indicates metabolism and
growth. The CO2 is quantitatively
detected by the BACTEC 460 system
instrument and is designated as Growth
Index (GI) increase or decrease in the
daily (GI) indicates increase or
inhibition of growth.
(C) Specimen collection:- Fluid from Douglas pouch was
collected using sterile technique to
reduce the chances of contamination of
the sample.
- To inoculate 13 A vials, the flip-caps
was removed from the vial top the
septum was swabed with alchol and the
specimen was aspectially injected.
- No prior processing of the sample was
needed; 5 ml was inoculated into each
13A vial.
- 13A Enrichment is provided in
separate vials, 0.5ml was added to each
13A vial to achieve optimal growth of
all mycobacteria.
- Inoculated vials were incubated at
37oC+ 1oC without shaking.
- Inoculated vials were then tested on a
BACTEC system instrument using 510% CO2 in air, Vials were tested
every 2-3 days for the first 2 weeks and
weekly there after for a total of six
weeks.
(D) Expected values:- The instrument reads out directly on a
Growth Index scale of 0-999 no
calculation were required.
- The Growth Index is actually a
measure of the metabolic activity of
organisms in the medium.
- When GJ reach 20 or more culture is
considered positive.
blood to be inoculated directly into
30ml of 13 A medium. Other body
fluids aseptically- collected may be
inoculated into this medium10.
PATIENTS AND METHODS:
150
infertile
women
undergoing laparoscopy were enrolled
into the study from December 2003 to
September 2005 in the departments of
Obstetric
and
Gynacology,
Microbiology and. Pathology, Minia
University hospital after a written
consent.
The cases included in the study
were, infertile aged between 20- 40
years in whom basic infertility workup
including complete history, general,
abdominal and pelvic examination,
semen analysis, hystrosalpingography,
day 21 serum progesterone was done.
During laparoscopy search for
TB criteria including pallor of the
tissues, retort shaped tubes, salpingitis
islhmica nodosa, eversion of the
fimbrial ends of the tubes, distal tubal
obstruction and scattered tubercles or
caseating material on pelvic peitoneum
or genital tract.
- Biopsy was taken from any suspected
lesion.
- Fluid from Douglas pouch was taken
for evaluation with BACTEC.
- System and culture in (L.J) medium.
- Endometrial curettings were obtained
for histopathology.
Sample processing for BACTEC:
(Becton, Dickinson and company
sparks, Maryland 21152 USA)
(A) BACTEC products required for
Mycobacterial culture:- BACTEC 460 TB system with a gas
tank containing 5-10% Co2 with
balance air.
- BACTEC 13A (Middle brook 7H 13)
medium.
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El-Adawy et al
________________________________________________________________________________
- As soon as the vial shows (GI) 20 or
more confirm the presence of
mycobacteria by the AFB smear (Acid
Fast Bacillus smear).
- When AFB are observed on smear
made from +ve vials specimen is
reported as culture positive for AFB.
- Negative results were reported after
six weeks.
uterine bleeding, only one cases with
adenexal mass and another one with
history of anti TB drugs as shown in
table II.
In the present study 11 cases
out of the 12 cases diagnosed by
laparoscopy were confirmed by tissue
biopsy, also 11 cases revealed positive
BACTEC, However only 8 cases were
positive for endometrial biopsy and
only 7 cases were positive by culture in
L J medium as shown in Table III.
RESULTS:
The incidence of genital TB in
the present study was 8% (12cases) the
highest incidence was noticed in the
age group (30-34) 6 cases, 8 cases
were from rural areas, 8 cases were not
educated and 8 cases were house wifes
as shown in table I.
Figure I (A.B.C) Shows the
receiver operating characterstic curve
(ROC) for studying sensitivity, specificity of different diagnostic modalities: both direct tissue biopsy and
BACTEC had the highest sensitivity
and specificity (93%-95%) followed by
endometrial biopsy (81%-83%) lastly
L J culture (72% -76%).
As regard clinical presentation
of the cases, 4 cases were presented
with history of pulmonary TB, 3 cases
with history of night fever and
sweating, 3 cases with abnormal
(Table I ): Patients characteristics of Participates
Variable
Age Group (years)
20-24
25-29
30-34
35-40
Residence
Urban
Rural
Educational
Non educated
Primary
Middle
University
Occupation
House wife
Worker
Higher occupation
Total
NO.
(150)
%
Diagnosed cases
(12)
15
35
70
30
10%
23.33%
46.66%
20%
2
3
6
1
60
90
40%
60%
4
8
90
30
20
10
60%
20%
13.33%
6.66%
8
2
1
1
100
40
10
150
66.66%
26.66%
6.66%
100%
8
3
1
8%
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El-Adawy et al
________________________________________________________________________________
(Table II): Clinical presentation of diagnosed cases having Genital T.B (12 cases)
Clinical data
History of pulmonary TB
“of night fever and sweating
Abnormal uterine bleeding
Adnexal mass
Anti TB drugs
NO.
4
3
3
1
1
%
33.33%
25%
25%
8.33%
8.33%
(Table III ) : Strength of positivity of different diagnostic tests for diagnosis of TB
95% C.I.
71-78.92
70-72.83
43.2-44.42
40.7-42.9
(A ) Direct Tissue Biopsy & BACTEC
1.00
.75
Sensitit
y




Variable
NO (%)
Odd ratio
11/12
619.4
Direct tissue biopsy
11/12
607.8
Positive BACTEC
8/12
403.9
Positive endometrial biopsy
7/12
382.7
Positive culture in L.J medium
Fig (I): ROC Curve For Different Diagnostic Modalities
.50
.25
0.00
0.00
.25
Specificity
108
.50
.75
1.00
AUC (Area Under the Curve)=
EL-MINIA MED., BULL., VOL. 17, NO. 1, JAN., 2006
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________________________________________________________________________________
(B) Endometrial Biopsy
1.00
Sensitity
.75
.50
.25
0.00
0.00
.25
.50
.75
1.00
AUC (Area Under the Curve)=
Specificity
(C) L.J Culture
1.00
Sensitity
.75
.50
.25
0.00
0.00
.25
Specificity
109
.50
.75
1.00
AUC (Area Under the Curve)=
EL-MINIA MED., BULL., VOL. 17, NO. 1, JAN., 2006
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________________________________________________________________________________
DISCUSSION:
TB once through to be a disease
of poor countries and nearly
completely eradicated in Western
world has resurged world wide and
become a global issue. It is the second
leading causes of death from infections
diseases (4% of all deaths) and 88
millions new cases of TB have
occurred throughout the world during
the last decade. Latent T.B is present in
two billion people and 7-8 million are
added each year. The prevelance of TB
in developed countries is mainly due to
rising incidence of HIV infection11.
from
rural
areas
where low
socioeconomic levels, poor health
education and bad housing are
prevelant, this is in agreement with
many studies which had been don in
Egypt (Nezar et al ., 2006) 14. m, Iran
(Mehrangiz, 2005)13 and India (Shahee
et al., 2006)11.
In the developing world instead
of HIV infection more important
promoting factors are poor case finding
and poor compliance of the patients
regarding dosage and duration of
therapy leading to drug resistance12.
In fact spread of TB occure in
early stages of the disease usually in
adolescence. By the time genital TB is
found the primary lesion in often
healed. Thus it is imperative to trace
past history of primary TB infection. It
has been reported that 50% of affected
women may give a past history of
exteragenital TB15 that is in agreement
with clinical presentation of our cases
where history of pulmonary TB was
the commenest presentation.
Genital TB is nearly always
secondary and the patient may be
unaware of primary focus most
commonly
pulmonary
lesion.
Moreover, it may recur despite early
recognition and effective treatment.
A report of the W.H.O shows
that there are at present 20million TB
patients in the world of whom 15
million live in the developing countries.
The number of deaths resulting from
TB is about 3 millions per years. At the
same time the annual incidence rate of
new TB cases is 2 million. Despite the
fact that the methods of treatment are
well known only one million are
successfully treated each year13.
As far as investigations for
genital TB are concerned histological
diagnosis is confirmatory with classics
picture of granuloma, central caseation,
Langhans gaint cells and lymphocytes.
In the present study the age
group (30- 34) is the most commonly
affected age for genital T.B, this is in
agreement with Schaffer et al., (1976)
and Jones et al., (1988) who found that
female genital TB is a disease of young
women with 80- 90% of patients first
diagnosed between the age of 20-40
years, however Hatchins study in 1977
showed that most patients belonged to
the age group 40-50years.
There have been major
advances in the filed of biotechnology
and
molecular
biology
with
introduction of several new diagnostic
techniques for TB and improvement in
existing ones. The new automated
culture techniques have appreciably
reduced the time for detection and anti
microbial testing. The molecular
amplification technique like PCR have
made the same day diagnosis a reality.
Introduction of new techniques like
bacteriophage assay are showing a lot
of promise17.
Geograhpic distribution of
genital TB in the present study
revealed that 8 cases (66.66%) were
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El-Adawy et al
________________________________________________________________________________
In the present study as shown in
(Table III) the diagnosis of genital TB
is as high with laparoscopy and direct
tissue biopsy as BACTEC and finally
endometrial biopsy and culture on L.J
medium.
endometrities in hills of Darjeeling: a
clinicopathological and bacteriological
study. Indian J palhol Microbiol 36,
361- 369. (Medline)
4- Shaaban.2002: Gynecology for
Postgraduates, Therapy and Practice.
Volume 1.
5- Dawn, C.S., Pelvic infection, In
Dawn C.S., Ed Textbook of Gynacology and Contraception: 1th Ed,
Calcutta, Arati Dawn, 1998, 321.
6- Aroar, V.K., Gupta, R. Arora,
R. (2003): Female genital tuberculosisneed for more research. Golden Jubilee
Contribution Indian Journal of Tuberculosis, 50:9.
7- Arora, V.K., Johri, A., Arora, R.
Rajarat, P., Tubercelosis of the vagina
in an HTV seropostive cases, Tubercle
lung Dis 1994, 75, 239.
8- Arora, R., Rajaram, P.,
Oumachigui, A. & Arora, V. K.:
prospective analysis of short course
chemolheropy in female genital tuberculosis. Int J Gynecol obstet 1992-38,
11.
9- Bates, J.H. (1979): Diagnosis
of tuberculosis. Chest76 (supply), 757763.
10- Itani, L.Y., Cherry, M.A. &
Araj, G.F. (2005): Efficacy of
BACTEC TB in the rapid confirmatory
diagnosis of mycobacterial infections.
A lebanese tertiary care center
experience. J Med Liban, 4: 208-12.
11- Shahee, R., Subhan, F. and
Tahir, F. (2006) Epidemiology of
genital tuberculosis in infertile population. Journal of Pakistan Medical
Association, 56(7):306-9.
12- Butt, T., Ahmed, R.N., Kazmi,
S.U., Raja, K.A. & Mohamed, A. An
update on the diagnosis of Tuberculosis. JC 2003, 13:728-34.
13- Mehrangiz, Hatami. (2005):
Tuberculosis of the female genital tract
in Iran. Arch Iranian Med, 8 (1):32-36.
14- Nezar, M., Anwar, K.& El
Negery,M. (2006). Genital tract
tuberculosis among infertile women
More over BACTEC showed
significantly shorter detection time of
isolates than L.J (means 9.6 days for
BACTEC versus 22.8 days for L.J).
So laparoscopic evaluation of infertile
women to rule out or to diagnosis TB
of genital tract is very essential. The
gold standard in diagnosis of genital
TB is finding characteristic caeseating
granulomas in biopsy.
CONCLUSION:
It is essential for gynecologist
working in developing countries to
anticipate possibility of genital T.B in
infertile patients.
For the diagnosis of genital TB
the simultaneous use of BACTEC and
L.J is recommended to provide
maximal optimal recovery of isolates
from clinical specimens.
The time saving in BACTEC
provides an excellent facility for
physicians in patient management.
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2- Parikh, F.R., Naik,N.,Nudkurni,
S.G., soon a wala, S.B., Komat, S.A.
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Bohattacharya, S., Adhya, S. and
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‫‪laparoscopic evaluation. Egyptian J.‬‬
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‫‪15- Bhann, N.V., Sungh, U.B.,‬‬
‫‪Chakraborty, M.& Suresh, N(2005):‬‬
‫‪Improved Diagnostic value of PCR in‬‬
‫‪the diagnosis of female genital TB‬‬
‫‪leading to infertility. J Med Micro‬‬‫‪biology, 45:927-31.‬‬
‫‪16- Khan, N. Frequency of endo‬‬‫‪metrial tuberculosis: a histopa‬‬‫‪thological study of endometrial‬‬
‫‪specimens 2005; 19:97-100.‬‬
‫‪17- Dam, P., Shirazee, H.H.,‬‬
‫‪Gozwami, S. K. & Ghosh, S. (2006):‬‬
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‫‪IVF failure use in the Indian clinical‬‬
‫‪setting. Gynecol Obstet Invest; 61:223-7.‬‬
‫تقييم الطرق المختلفة لتشخيص دور الجهاز التناسلي في‬
‫السيدات الالتي يعانين من العقم‬
‫أحمد رضا العدوى* – محمد إبراهيم بسيونى** – وفاء فرغلى***‬
‫أقسام *النساء والتوليد ‪** -‬الميكروبيولوجى ‪*** -‬الباثولوجى‬
‫كلية طب المنيا‬
‫تهد الدر سد ددحلدرة رلددحلدرددنلتة ل د ل د حلد د حل د سالدراهد لدرت د نل ددنلدر ددل د ل‬
‫درالتنللع لالمالدرعقملوذركلأث ءلداسدءلدرم ظد سلدر ن د لرهدالوكدذركلتهد الدردنلتقلدلملدرندس ل‬
‫درمخت فحلرتشخلصل سالدراه لدرت نل‪.‬ل ل‬
‫أاسل لهذهلدر سد حل نلأق ملأمدسد لدر د ءلودرتورلد لودرملكسو لوردوانلودر د ثوروانل‬
‫ك لحلنبلدرم لد ل دنلدرفتدس لمدال ل دم سل‪2003‬لوةتدنل د تم سل‪2005‬ملوضدم ل‪150‬لمسلضدحل‬
‫لع لالمالدرعقملتملعمللدرفةوصلدرال محلرهملوأث ءلعمللدرم ظ سلدر نالدرتشخل نلتدملتة لد ل‬
‫ةد ت لد د حل هددذدلدرمدس لوتددملدخددذلعل ددحلمدالأ لد د حلمتوقعددحلوكددذركلتدملدخددذلعل ددحلمددال‬
‫در د للدرمواددو ل ددنلالددبل واددال لر د س لع د لم سعددحل(ل‪-‬ج)لوكددذركلدرعددس لع د لاهد ل‬
‫در كتلكلودخلسدلتملدخذلعل حلمال ن حلدرسةملر عس لدر ثوروانل‪.‬ل‬
‫أظهس لدر ت جلأال حلتشخلصل سالدراه لدرت نل رم ظ سلت للدرنل‪%8‬لوك ل‬
‫درغ ر لحلدرغ ر لحل لال ك الدرقسىلودر ل د لذولدرم تو لدرمعلشنلودرتع لمنلدرم خف لوأظهدس ل‬
‫در سد دحلأالدرفةدصلدر د ثوروانلر عل دحلدرمدخخوذ لمددالدت داحلدرمتوقد لد د ته ل رد سالوكددذركل‬
‫درفةددصل ر كتلددكلمددالدة دد لحلة رلددحلمددال ةلددحلدرة ددحلودرخ و ددلحلل ددنلذرددكلدرعددس ل‬
‫در ثوروانلر ن حلدرسةملودخلسدللختنلدر س لع لم سعحل(ل‪-‬ج)ل‪.‬ل‬
‫حل ر سال نلدةتم تتد ل‬
‫خ صلمالذركلدرنلأهملحلأاللض لاسدحلدر ءلودرتورل لد‬
‫ع لداسدءلم ظ سلدر نالدرتشخل نلرة ت لدرعقملودرنلأالدرفةصل ر كتلكلرد لقلمدحلدة د لحل‬
‫ع رلحل نلدرتشخلصلولقوملدرم دس لدتخس لر سال نلق لدروق لدرال ملر تشخلصل ل‬
‫‪112‬‬