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Female genital tuberculosis

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DOI: 10.1576/toag.7.2.075.27000

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Female genital tuberculosis REVIEW

The Obstetrician
David K Gatongi, Godfrey Gitau, Vanessa Kay, & Gynaecologist
Solwayo Ngwenya, Cyril Lafong, Adnan Hasan
2005;7:75–79
Tuberculosis affects a large number of people worldwide and the
incidence is increasing. Tuberculosis bacilli reach the genital tract
mainly by haematogenous spread from foci outside the genitalia. The Keywords
fallopian tubes, endometrium and ovaries are affected in most cases. anti-tuberculous
Genital tuberculosis may be asymptomatic and could go unrecognised chemotherapy,
or masquerade as other gynaecological conditions. A combination of genital tuberculosis,
HIV, infertility,
tuberculin testing, culture, histology, hysterosalpingogram and nucleic tuberculosis
acid amplification testing is useful in establishing a diagnosis.
Multidrug anti-tuberculosis chemotherapy is the mainstay of
treatment. After treatment spontaneous conception is low with an Author details
increased risk of ectopic pregnancy and spontaneous miscarriage.

Introduction In the UK, the overall TB rate is increasing. A

Tuberculosis (TB) is an increasing public health
concern worldwide, with about six million new
cases a year. It is one of the most important causes
of infectious morbidity and mortality. On a global
scale, TB has a devastating impact in developing
nations with 13 countries accounting for nearly
75% of all cases.1 TB exists in two forms:
pulmonary tuberculosis and extrapulmonary
tuberculosis. Genital TB is one form of
extrapulmonary TB and is not uncommon,
particularly in communities where pulmonary TB
is prevalent, but it is rare in Western societies.This
is evidenced by the paucity of literature on this
subject in developed countries as compared with
rate of 12.9/100 000 was reported in 2002,
which is an increase of 4% on the 2001 rate.This
upward trend has been evidenced since 1988 in David K Gatongi MRCOG,
Specialist Registrar, Dumfries and
England and Wales,7 while the overall incidence Galloway Royal Infirmary, Bankend
in Scotland has remained stable over the last 10 Road, Dumfries DG1 4AP, UK
e-mail: davidspax@yahoo.com
years. This increase is attributed to increasing (corresponding author)
migrants from high prevalence countries, rising
HIV infection rates, homelessness, drug abuse
and emergence of multidrug resistant strains of
TB bacilli. Similar trends have been reported in
the USA.1,7
The surge in TB rates in the UK has been Godfrey Gitau MRCOG, Specialist
characterised by an increase in the ratio of Registrar, Royal Victoria Infirmary,
extrapulmonary to pulmonary TB, with Newcastle upon Tyne, UK

less developed countries. Genital TB affects about
12% of patients with pulmonary tuberculosis2 and
represents 15–20% of extrapulmonary
tuberculosis.3 Genital TB may be asymptomatic
and diagnosis requires a high index of suspicion.
Moreover, the disease may masquerade as other
gynaecological conditions and can go
unrecognised.4 Multiple drug chemotherapy,
comprising isoniazid, rifampicin, ethambutol and
pyrazinamide, is the mainstay of treatment.
Epidemiology
The actual incidence of genital TB in the general
population cannot be accurately determined, as
some patients are asymptomatic and may remain
undiscovered.5 It is estimated to affect 1.5/100
000 inhabitants in the UK. Worldwide, genital
TB is found in 5-10% of women with infertility
problems,6 with low rates in Australia (1%) and
high rates of up to 19% in India.5
extrapulmonary TB representing 40% of all TB
cases in 2001 compared with 33% in 1988.7
Within England,Wales and Northern Ireland,TB
infection rates vary between regions and
different population groups. There is a strong
urban association with London, the Midlands Vanessa Kay MD MRCOG,
and the North West accounting for over 70% of Consultant Obstetrician and
Gynaecologist, Ninewells Hospital,
cases. The rate in London is the highest at Dundee, Scotland, UK
41/100 000.7 Among population subgroups the
rate was highest in black Africans (272/100 000)
followed by Indian, Pakistani and Bangladeshi
ethnic groups (124/100 000).7
HIV has altered the dynamics of TB worldwide.
Between 1993 and 1998, the numbers of
Solwayo Ngwenya DFFP
tuberculosis patients co-infected with HIV in MRCOG, Specialist Registrar,
England and Wales, although small, had nearly Huddersfield Royal Infirmary,
Huddersfield, UK
doubled from 61 (2.2%) to 112 (3.3%).8 Patients
co-infected with HIV contributed about 8.5% of Cyril Lafong BAO FRCPath,
Consultant Microbiologist, Victoria
the increase in tuberculosis cases.8 Extrapulmonary Hospital, Kirkaldy, Scotland, UK

75
2004 Royal College of Obstetricians and Gynaecologists
© 2005
 REVIEW TB is more common in HIV-positive patients,9
The Obstetrician and in African countries, 60–90% of patients with
& Gynaecologist extrapulmonary TB are HIV-positive.9
2005;7:75–79 Microbiology and pathology
Mycobacterium tuberculosis accounts for 90–95% of
cases of genital TB. However, Mycobacterium bovis
Author details may be the causal agent (5–10%), especially
when the organisms are acquired from the
gastrointestinal tract.1,5
TB bacilli are spread from person to person by the
inhalation of aerial droplets produced by coughing,
sneezing and talking.1 Infection by oral ingestion is
rare, as is transmission by sexual intercourse.5,10
Adnan Hasan MSc MRCOG,
Hospital Specialist, Forth Park TB of the female genital tract is nearly always
Hospital, Kirkaldy, Scotland, UK
secondary to a focus elsewhere in the body.11 The
TB bacilli reach the genital tract by three principal
routes. Haematogenous spread represents about
90% of cases, with the primary focus being the
lungs, lymph nodes or skeletal system. Descending
direct spread occurs, with infection reaching the
genital organs via the lymphatic system or directly
from the gastrointestinal tract, mesenteric nodes or
the peritoneum.3
Primary infection of the vulva, vagina and cervix
may result from direct inoculation at sexual
intercourse with persons having genitourinary
TB. Ascending spread of infection from the
vagina, cervix and the vulva may occur.5,10
Genital organs commonly involved include the
fallopian tubes (95–100%) endometrium
(50–60%) and ovaries (20–30%). The cervix
(5–15%), vulva/ vagina (1%) and the
myometrium (2.5%) may also be involved.3,11
Haematogenous spread of TB bacilli to the tubes
results in involvement of the submucosa
(endosalpingitis) at the outer ends with gradual
spread medially to the endometrium. Direct
spread of infection to the fallopian tubes results
in exosalpingitis with tubercles on the surface.3
The appearance of genital organs infected with
TB can vary: in some, the tubes may appear
normal. During active infection they appear red
and oedematous and in chronic infection they
appear fibrosed. Tubal obstruction may result in
pyosalpinx or hydrosalpinx. Extensive pelvic
adhesions may result.6 Endometrial involvement
may result in an endometrial ulcer or
accumulation of caseous material to form
pyometra. Intrauterine adhesions and partial
obliteration of the uterine cavity may also occur.3
The endometrium may be proliferative (37%),
secretory (18%), mixed (11.7%) or hyperplastic
© 2004 Royal College of Obstetricians and
76 Gynaecologists
(3.7%)12 TB may therefore have a pathogenic
role in abnormal uterine bleeding.
Clinical presentation
Although genital TB can occur in any age group,
the majority of patients are in the reproductive
age group, 75% being in the 20–45 years age
bracket.11 Postmenopausal women account for
7–11% of cases of genital TB.
Genital TB may be asymptomatic and the majority
of women are diagnosed during investigations for
infertility.6,9 Systemic constitutional symptoms of
weight loss, feeling unwell and night sweats may be
present. In the acute phase, the picture may
resemble classical acute pelvic inflammatory
disease (PID)9 with pelvic pain, fever and vaginal
discharge. Fitz-Hugh Curtis syndrome may result
from tuberculous PID.
Genital TB may present with a variety of
gynaecological symptoms of infertility, menstrual
disturbance and chronic pelvic pain (Table
1).11,13,14 In the postmenopausal woman, genital
TB presents with postmenopausal bleeding,
persistent leucorrhoea and pyometra.13,15
Tuberculous lesions of the cervix present with
postcoital bleeding, abnormal discharge and, on
examination, have appearances similar to cancer of
the cervix.10 Lesions on the vulva appear as
shallow ulcers, which may be painful, especially
with secondary bacterial infection.Vaginal lesions
are often painless and are usually sited at the
introitus. Both can result in bloodstained purulent
discharge and may be identified as sexually
transmitted infection.16 The Bartholin’s gland may
be affected, presenting with pain and fistula
formation despite adequate antibiotic cover.
Involvement of the ovaries may result in an adnexal
ovarian mass. Fistula formation to the bowel, skin
or vagina may be seen. Peritoneal involvement may
give rise to ascites.This, in addition to an adnexal
mass and a raised serum CA125 level, can be
mistaken for ovarian cancer and can result in
unnecessary surgical intervention.4 Occasionally,
Table 1. Presenting symptoms
Symptom Percentage of total
Infertility 43–74
Primary 55–78
Secondary 11–72
Normal menstrual function 50–88
Oligomenorrhoea 54
Amenorrhoea 14
Menorrhagia 19
Abdominal pain 42.5
Dyspareunia 5–12
Dysmenorrhoea 12–30
pleural effusion in association with a pelvic mass fits
into the picture of Meigs’ syndrome.
General, abdominal and pelvic examination
findings are normal in majority of genital TB
patients.2,14 A pelvic mass may be identified and
adnexal tenderness may be elicited.
Diagnosis
Diagnosis is achieved most effectively through
a combination of a high index of suspicion,
especially in areas of low prevalence, thorough
initial clinical assessment and the use of
appropriate investigations. High risk factors
include a history of previous pulmonary TB
infection, contact with a pulmonary TB
sufferer, recent travel to or migration from high
prevalence countries, residence in high
prevalence areas such as London, low
socioeconomic background, drug abuse, HIV
positive status and history of chronic chest
symptoms, night sweats and weight loss.
Individuals of black African and Asian descent
are high-risk race groups.1,5,6
Tuberculosis should be considered in a woman
with high risk factors presenting with
unexplained infertility, amenorrhea not
explained by other causes, pelvic infection that
does not respond to ordinary treatment and, in
postmenopausal women with bleeding,
persistent leucorrhoea and pyometra where
endometrial neoplasia has been excluded.
Investigations
Although demonstration of the TB bacilli
confirms the diagnosis, other indirect tests are
useful.A full blood count is often normal but the
erythrocyte sedimentation rate is usually raised.1
With increasing numbers of TB patients being
co-infected with HIV, testing for HIV is
recommended for all patients with genital TB.9
The tuberculin skin test has a sensitivity of 55%
and specificity of 80% in patients with genital
tuberculosis.17 False-positive reactions do occur
and represent non-tuberculous mycobacterium
infections. False-negative reactions, although
uncommon in otherwise healthy patients with
tuberculosis, occur in at least 20% of patients
with known active tuberculosis. HIV infection
and corticosteroid therapy may cause false-
negative test results.1
Chest X-ray is aimed at demonstrating current
or past tuberculous lesions in the lungs, which
are a common site for primary infection.
However, most chest X-rays are normal.
© 2004 Royal College of Obstetricians and
Gynaecologists
Whenever feasible, every effort should be made to REVIEW
send specimens and tissue for culture, in order to
The Obstetrician
confirm diagnosis and establish drug sensitivities.
& Gynaecologist
Suspected tuberculous lesions in accessible sites
such as the vagina, cervix and the vulva may be
2005;7:75–79
biopsied directly. Endometrial tissue may be
obtained by aspiration biopsy or by dilatation and
curettage or directly at hysteroscopy. Endometrial
biopsy is best performed in the premenstrual
period. Menstrual fluid can be obtained from the
vagina during the first day of menstruation for
culture and microscopy.18 Less accessible lesions
on the tubes, ovaries and adnexae can be obtained
at laparoscopy or laparotomy. Laparoscopic
findings include adhesions, tubal abnormalities
and ascites.6
Histology demonstrates the typical caseous
granulomatous lesions with giant epithelioid
cells (Figure 1). This lesion is highly suggestive
of TB but is not diagnostic, as it appears in
fungal infections and sarcoidosis. Microscopy for
alcohol and acid-fast bacilli (AAFB) can provide
a quick diagnosis (Figure 2). Fluorescent
auramine-phenol and Ziehl-Neelsen (Z-N)
staining can be performed on endometrial
aspiration biopsy.
Culture on solid media, such as egg-based
Löwenstein-Jensen medium, can give positive
results for M. tuberculosis in 4 weeks but can take
up to 12 weeks. Liquid culture with radiometric
growth detection such as BACTEC-460 or non-
radiometric (CO2) growth detection such as
BacTAlert 3D, provides more rapid growth
(average 10–14 days), specific identification of
Figure 1. Granulomatous
M. tuberculosis and rapid drug susceptibility
testing to guide therapy.1 lesion in a woman with
endometrial TB
77
 REVIEW Rapid nucleic acid amplification techniques such
as polymerase chain reaction (PCR) allow direct
The Obstetrician
identification of M. tuberculosis in clinical
& Gynaecologist
specimens. Such methods can detect fewer than
ten organisms in clinical specimens compared with
2005;7:75–79
10 000 necessary for smear positivity, an important
Figure 2. Ziehl-Neelsen feature because genital TB is paucibacillary with
staining showing AAFB cultures and smears usually being negative.
cultured from
Although PCR is more sensitive (85–95%) than
endometrial curettings
microscopy and bacteriological culture on
pulmonary and extrapulmonary specimens, it does
not distinguish live from killed bacilli.1,19
Imaging
Abdominal and pelvic ultrasound, computed
tomography (CT) and magnetic resonance
imaging (MRI) are employed in circumstances
where an abdominal or pelvic mass is present.
They are also useful in the presence of ascites
where malignancy is a possibility.
Sonographic features of wet tuberculosis (with
ascites) include septated ascites, particulate ascites,
loculated fluid, thickened peritoneum, thickened
omentum, endometrial involvement and adnexal
masses. Features of dry tuberculosis (no ascites)
include adnexal masses, adhesions and loculated
fluid. When compared with laparoscopy/
laparotomy, ultrasound was able to identify
ascites/loculated fluid (100%), adnexal masses
(93%), peritoneum thickening (69%), omental
thickening (61%), and endometrial thickening
(83%). Awareness of these features may improve
diagnostic accuracy and avoid misdiagnosis and
unnecessary surgical intervention.20
CT findings of abdominal tuberculosis may
mimic diffuse peritoneal malignancy. These
78
© 2004 Royal College of Obstetricians and Gynaecologists
features include ascites, omental and mesenteric
infiltration and smooth thickening of the parietal
peritoneum.21
Hysterosalpingogram
Hysterosalpingogram (HSG) is performed
frequently22 as an investigation for infertility, this
being a common presentation of genital TB. It
should not be performed where TB is diagnosed
by other means, as it may result in dissemination
and flare-up of disease.23 Tubal occlusion is the
most common HSG finding in genital
tuberculosis. Occlusion occurs most commonly
at the junction between the isthmus and
ampulla. Multiple constrictions along the tube
give the ‘beaded’ appearance on HSG, while
scarring gives the ‘rigid pipe system’ appearance.
Tubal dilatation, hydrosalpinx, irregular tubal
outline and calcifications are other features that
can be identified on HSG. Chavhan et al.22
reported TB in 7.5% of HSGs performed for
infertility in a series of 37 patients. The HSG
features identified included tubal occlusion in 30
women, rigid pipe appearance in nine, tubal
dilatation in 17, irregularity of the tube in 6 and
peritubal adhesions in 11 of the women.
Endometrial tuberculosis has been reported to
have nonspecific features on HSG, commonly
characterised by synechiae, distorted uterine
contour and venous and lymphatic intravasation.
Scarring of the uterus may lead to unilateral
obliteration of the uterus, giving rise to
unicornuate appearance ‘pseudounicornuate
uterus’ or conversion of the uterine cavity into a
T-shape or an asymmetric small uterus.
Synechiae were seen in six patients and venous
and lymphatic intravasation in 10 of 37 patients
in the study by Chavhan et al.22
Although the various features that HSG
describes are not specific for genital tuberculosis,
they are highly suggestive of it.
Treatment
It is essential that physicians and microbiologists
experienced in TB management are involved in
the treatment of genital TB. Six-month regimens
including four drugs in the initial phase
(rifampicin, isoniazid, pyrazinamide and
ethambutol) followed by rifampicin and
isoniazid in the continuation phase are highly
effective in patients with fully sensitive
organisms. Combined therapy enhances
compliance and reduces the risk of secondary
drug resistance. Relapse after treatment is seen in
0–3% of cases. All anti-tuberculous drugs can
cause adverse reactions; these are seen in about
10% of patients and are common in HIV-positive
patients. Isoniazid and rifampicin both are
associated with hepatitis, cutaneous
hypersensitivity and haemolytic anaemia. Isoniazid
may cause peripheral neuropathy. Pyrazinamide
causes anorexia, nausea, hepatitis, arthralgia and
hyperuricaemia. Ethambutol is associated with
retrobulbar neuritis, hepatitis and peripheral
neuropathy. Monitoring visual acuity for those
taking ethambutol is therefore necessary. Liver
function should also be monitored.24
The incidence of multi-drug resistant strains of
TB bacilli is increasing worldwide mainly as
result of under-treatment. In the UK, 1.2% of TB
isolates were found to be multi-drug
resistant.25,26 Multi-drug resistance in the UK is
commonly seen in young men, people not born
in the UK, HIV-positive patients and people
with a previous history of TB.25,26 It is therefore
absolutely essential that compliance be ensured.
The World Health Organization advocates a
strategy of direct observation of therapy to
improve cure rates and minimise the
development of drug resistance.1,26
Although chemotherapy is the mainstay of
treatment, surgery may be indicated where
medical therapy has failed to resolve symptoms
and in presence of a persistent pelvic mass. In
these circumstances, total abdominal
hysterectomy is the operation of choice, while
bilateral salpingo-oophorectomy may be
considered if the ovaries are severely
involved.5,6,27 Adhesiolysis may be performed for REVIEW
chronic pelvic pain. The Obstetrician
& Gynaecologist
After treatment for genital TB, the conception rate
is low (19.2%) with a livebirth rate of 7.2%.There is 2005;7:75–79
also an increase in ectopic pregnancy and
miscarriage rates. In vitro fertilisation should
therefore be offered to those who fail to conceive
spontaneously.23
Conclusion
The incidence of female genital TB is increasing,
so gynaecologists will be increasingly faced with
cases of TB and its consequences. Genital TB may
be asymptomatic or may present with atypical
symptoms or mimic other conditions. It is
imperative to consider the possibility of TB in
women in the reproductive age group who
present with the symptoms of infertility, chronic
pelvic pain and menstrual dysfunction, where
other causes have been excluded. This is
particularly important when these women fall into
the high-risk category for TB infection. Genital
TB should also be considered in postmenopausal
women with pyometra and persistent vaginal
discharge.
Failing to consider the possibility of TB may result
in unnecessary and ineffective interventions. To
increase the chances of identifying TB bacilli,
immunological, bacteriological and nucleic
amplification tests should be employed, as they are
complementary. ■

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© 2004 Royal College of Obstetricians and Gynaecologists

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