International Journal of Infectious Diseases 73 (2018) 60–62

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International Journal of Infectious Diseases

journal homepage: www.elsevier.com/locate/ijid

Case Report

First case of sexually transmitted asymptomatic female genital

tuberculosis from spousal epididymal tuberculosis diagnosed
by active screening
Muneyoshi Kimuraa,* , Hideki Araokaa,b , Hiromi Babaa , Chikako Okadaa ,
Yoshiro Murasec , Akiko Takakic , Satoshi Mitaraic , Akiko Yoneyamaa
a
Department of Infectious Diseases, Toranomon Hospital, Tokyo, Japan
b
Okinaka Memorial Institute for Medical Research, Tokyo, Japan
c
Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose, Tokyo, Japan

A R T I C L E I N F O A B S T R A C T

Article history:
Received 5 April 2018 Tuberculosis screening was performed for a healthy asymptomatic woman to determine whether she had
Received in revised form 24 May 2018 been infected with active genital tuberculosis via sexual intercourse with her husband who had
Accepted 29 May 2018 epididymal tuberculosis. Vaginal swab culture yielded Mycobacterium tuberculosis. Furthermore, whole
Corresponding Editor: Eskild Petersen, Aar- genome sequencing revealed that the two causative isolates were genetically identical. This appears to be
hus, Denmark
the first report on the sexual transmission of genital tuberculosis from a man to an asymptomatic woman,
detected by active screening for genital tuberculosis and molecular analysis, including whole genome
Keywords: sequencing. Active screening for genital tuberculosis in the female partner should be considered soon
Sexual transmission
after diagnosis of male genital tuberculosis, even when the female partner is asymptomatic.
Genital tuberculosis
© 2018 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
Tuberculosis
Screening This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
Epididymal tuberculosis nc-nd/4.0/).

Introduction Case reports

Female urogenital tuberculosis comprises approximately 0.5% Patient 1 (index case)

of all tuberculosis cases, and among urogenital cases, less than
50% are genital tuberculosis cases (Neonakis et al., 2011; Cookson
et al., 2008). Urogenital tuberculosis is usually secondary to
hematogenous spread from a primary focus, typically in the lung
(Schlossberg, 2011). However, primary female genital tuberculo-
sis might develop after sexual intercourse with a male partner
who has tuberculosis of the penis or epididymis (Schlossberg,
2011; Angus et al., 2001). The possibility of sexual transmission
has also been suggested by an animal model (Gondzik and
Jasiewicz, 1979a,b). Nevertheless, the effectiveness of active
screening for an asymptomatic female sexual partner soon after
the diagnosis of male genital tuberculosis has not been reported
to date.
* Corresponding author at: Department of Infectious Diseases, Toranomon
Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.
E-mail address: muneyoshi-k@toranomon.gr.jp (M. Kimura).
A 54-year-old man noticed a swelling of the right epididymis
approximately 3 years before the diagnosis of epididymal
tuberculosis. He was initially considered to have acute epididymi-
tis. Although the causative organism could not be identified by
urine testing, he was prescribed oral levofloxacin. The swelling of
the epididymis recurred several times and was relieved by
levofloxacin each time. However, approximately 1.5 years before
the diagnosis, the left epididymis also started to swell gradually. A
left orchiectomy was performed, because a tumor of the
epididymis was suspected. Pathological findings of the resected
testis revealed multinucleated giant cells and numerous caseous
granulomas. He was referred to the Department of Infectious
Diseases because tuberculosis was highly suspected. Subsequently,
he was diagnosed with epididymal tuberculosis based on urine
PCR, urine culture, and histopathological findings. Additionally, a
T-SPOT.TB test (Oxford Immunotec, Oxford, UK) and HIV antibody
test were both negative. Findings on chest computed tomography
(CT) scan were unremarkable except for calcification of a
mediastinal lymph node. He had been diagnosed with breast
cancer 10 years earlier, which had been resected; there had been

https://doi.org/10.1016/j.ijid.2018.05.021
1201-9712/© 2018 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/).
 M. Kimura et al. / International Journal of Infectious Diseases 73 (2018) 60–62
no recurrence at the time of presentation. The Mycobacterium
tuberculosis isolated was susceptible to isoniazid, rifampicin,
pyrazinamide, ethambutol, levofloxacin, and streptomycin. Treat-
ment was commenced with isoniazid, rifampicin, pyrazinamide,
and ethambutol for 2 months, followed by isoniazid and rifampicin
for a further 4 months.
Patient 2 (infected spouse)
A 53-year-old woman visited the outpatient clinic of the
Department of Infectious Diseases at Toranomon Hospital with
her husband (patient 1) to inquire about the possibility of sexual
transmission of tuberculosis approximately 1 month after his
diagnosis. They were worried, although she looked healthy and
had no symptoms: no fever, night sweats, weight loss, pelvic or
abdominal pain, menstrual disorder, or respiratory symptoms
including dyspnea and cough. She had been having unprotected
sexual intercourse with her husband once a week until 6 months
before the diagnosis of epididymal tuberculosis. However, she
had then refrained from sexual intercourse with her husband
when they noticed the apparent swelling of his left epididymis
because she was afraid of contracting a sexually transmitted
infection from him. She had no past history of illnesses or
operations, except for migraine at about 20 years of age and
bilateral tubal ligation at about 35 years of age after the delivery
of their third child. She reported having no other sexual partners
after marriage. Finally, it was decided to perform active screening
for genital tuberculosis even though she was asymptomatic.
Laboratory findings of blood and urine testing were unremark-
able. A T-SPOT.TB test and HIV antibody test were both negative.
Chest and abdominal CT scans that included the pelvic area were
unremarkable. Furthermore, a pelvic examination and transvagi-
nal ultrasound performed by a gynecologist were unremarkable
except for a right ovarian cyst. A biopsy was not performed
because no abnormal findings were observed in the endocervical
canal or endometrium at that time. However, vaginal swab
culture yielded M. tuberculosis and she was diagnosed with genital
tuberculosis. Treatment for tuberculosis was started with the same
regimen as that of her husband.
Both M. tuberculosis isolates were sent to the Research Institute
of Tuberculosis (Tokyo, Japan) for further analysis. Variable
number tandem repeat analysis (VNTR, 24 loci) showed that the
organisms from the two cases were identical (Iwamoto et al.,
2012). Further analysis by whole genome sequencing (WGS;
MiSeq, Illumina) confirmed that the two isolates were genetically
identical with only one nucleotide difference (Sekizuka et al.,
2015).
Discussion
In a retrospective study of 128 male partners of women who
were diagnosed with genital tuberculosis, five male partners (3.9%)
had been diagnosed with genitourinary tuberculosis before their
female partners were diagnosed, indicating the possibility of
sexual transmission (Sutherland et al., 1982). In addition, a
previous case report described a female patient with menorrhagia,
fever, sweats, and weight loss, diagnosed with endometrial
tuberculosis 1 year after her husband’s diagnosis of tuberculosis
of the penis (Angus et al., 2001). Furthermore, the causative strains
of M. tuberculosis were confirmed to be indistinguishable on
molecular analysis (Angus et al., 2001).
In the previous reports, there was an interval of 1 year or more
between the diagnosis of the husband and the diagnosis of genital
tuberculosis in the wife (Angus et al., 2001; Sutherland et al., 1982;
Richards and Angus, 1998). It appears that this is the first report on
the sexual transmission of genital tuberculosis from a man to an
61
asymptomatic woman that was detected by active screening for
genital tuberculosis soon after his diagnosis and confirmed using
molecular analyses, including WGS. WGS analysis is superior to the
genotyping methods used in the previous report (Angus et al.,
2001). Furthermore, a previous study established that most
M. tuberculosis isolates were within five single nucleotide
polymorphisms on the genome of another isolate obtained from
the same individual or from a household contact (Walker et al.,
2013). Therefore, in the present study, the causative strains of M.
tuberculosis were strongly considered to be identical. Also, the
possibility of air-borne transmission in these cases was considered
to be low because there was no evidence of active pulmonary
tuberculosis, including respiratory symptoms and findings on
chest CT.
Few reports on sexual transmission have been published to
date, although tuberculosis is one of the most common infectious
diseases worldwide (Angus et al., 2001; Sutherland et al., 1982;
Richards and Angus, 1998). Furthermore, it seems that active
screening of a female partner has not typically been performed
when male genital tuberculosis has been diagnosed. Thus, the
possibility of sexual transmission might have been underesti-
mated. Another potential reason why few reports of sexual
transmission are available is that the possibility of sexual
transmission of M. tuberculosis to female partners may be
extremely low, although the possibility of sexual transmission of
M. tuberculosis in the semen of men with urogenital tuberculosis
has been reported (Neonakis et al., 2011; Lattimer et al., 1954). In
the present cases, frequent contact between semen and the female
genital tract probably occurred for a long time due to unprotected
sexual intercourse after bilateral tubal ligation. This might explain
why sexual transmission occurred in these cases.
Female genital tuberculosis, which is commonly implicated as
a cause of infertility (Punnonen et al., 1983; Nogales-Ortiz et al.,
1979), remains a major health problem, especially in developing
countries (Muir and Belsey, 1980). In fact, among women
presenting to infertility clinics in the USA, less than 1% were
recorded as female genital tuberculosis cases, whereas the rates
were found to be high (ranging from 4.2% to 21%) in developing
countries (Neonakis et al., 2011). Early diagnosis is critical,
because M. tuberculosis infection is associated with fibrosis of the
female genital organs, and once this fibrosis is established, it is
difficult to restore fertility even if the patient receives appropriate
treatment (Neonakis et al., 2011; Lamba et al., 2002). Therefore,
active screening for genital tuberculosis in the female partner
should be considered soon after a diagnosis of male genital
tuberculosis to ensure an early diagnosis, even when the woman is
asymptomatic.
This appears to be the first report on the sexual transmission of
genital tuberculosis from a man to an asymptomatic woman
detected by active screening for genital tuberculosis and whole
genome sequencing.
Acknowledgements
We thank the staff of the Microbiology Laboratory of
Toranomon Hospital for performing the tests for the identification
of the Mycobacterium tuberculosis.
Funding
None.
Conflict of interest
The authors report no conflicts of interest. The authors alone are
responsible for the content and writing of the paper.
62 M. Kimura et al. / International Journal of Infectious Diseases 73 (2018) 60–62
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