International Journal of STD & AIDS 2000; 11: 548± 550

CASE REPORT

Adenovirus and non-gonococcal urethritis

S Azariah MBChB and M Reid MBChB FACSHP
Auckland Sexual Health Service, Auckland Healthcare Services, Private Bag 92 024,
Grafton, Auckland 1, New Zealand

Summary: Non-gonococcal urethritis (NGU) is a common problem presenting to

sexual health clinics that is usually managed empirically. In many cases the
aetiology is never clearly established or further investigated. Adenovirus has been
identi® ed in the past as an occasional cause of NGU but little has been written about
its clinical presentation. We present a case report of 6 men who were diagnosed
with NGU caused by adenovirus infection, along with a review of the relevant
literature, with the aim of improving clinical recognition of this pathogen.
Keywords: Adenovirus, non-gonococcal urethritis, sexually transmitted infection

INTRODUCTION likelihood was due to genital infection with

Non-gonococcal urethritis is a commonly diag-
nosed syndrome in sexual health clinics. Various
organisms have been proven, or postulated, to play
a role in the pathogenesis of this syndrome
including Chlamydia trachomatis, Ureaplasma urealy-
ticum, Mycoplasma genitalium and Trichomonas
vaginalis. The evidence for pathogenicity for some
of these organisms is stronger than for others. A
pathogen that has seldom been the focus of
attention in the past as a cause of NGU is
adenovirus.
Adenoviruses were ® rst discovered by Rowe et
al.1 in 1953 when they were isolated from a surgical
specimen of adenoidal tissue. Since then about 40
different serotypes have been identi® ed. Adeno-
viruses have been linked to a variety of clinical
syndromes, for example, upper respiratory tract
infections, urinary tract infections in children,
infantile diarrhoea, central nervous system (CNS)
infections and epidemic keratoconjunctivitis1. It
would therefore appear highly plausible that they
could also cause in¯ ammation of genital tract
mucosa.
Adenoviruses have indeed been isolated from
genital sites in the past. Laverty et al.2 reported a
case of adenoviral infection of the cervix in 1977.
Harnett and Newnham3 reported isolation of
adenovirus from 13 males with NGU in 1981. It
becomes however more dif® cult to make the leap
from the knowledge that an organism is capable of
colonizing the genital tract, towards implicating it
in the pathogenesis of a syndrome such as NGU.
The following are a series of case histories of 6
men presenting with urethritis to the Auckland
Sexual Health Centre in recent years, which in all
Correspondence to: Dr Sunita Azariah
548
adenovirus (Tables 1 and 2).
DISCUSSION
In summary we have presented 6 cases of men with
NGU from whom adenovirus was cultured from
genital sites, with no other pathogen identi® ed. All
6 men presented with a history of dysuria (mean
duration 12.8 days), symptoms of conjunctivitis,
respiratory tract infection or malaise, and a history
of oral insertive sex. Five out of 6 cases were men
who have sex with men; none were HIV infected.
There also appeared to be no obvious seasonal
pattern to infection. Routine microscopy did not
always ® t standard criteria for diagnosis of
urethritis as elevated numbers of polymorpho-
nuclear cells were not always present. However, in
some cases large numbers of mononuclear cells
were noted. A mononuclear cell response has been
previously noted in some cases of urethritis caused
by herpes simplex virus (HSV) 4.
All cases had a sub-optimal response to standard
empirical tetracycline therapy for NGU. The 4 cases
treated empirically with a thymidine kinase
inhibitor for possible HSV urethritis also res-
ponded poorly to therapy. This would support
the hypothesis that it was adenovirus, and not
undiagnosed chlamydia or HSV, that was respon-
sible for their genital symptoms.
It is reassuring to note that in those men who did
present for follow up, symptoms appeared to be
self-limiting.
Adenovirus is not routinely screened for in cases
of NGU at our service. These men were identi® ed
either because viral cultures were performed to test
for suspected HSV infection, (the virology labora-
tory will perform further investigations for con-
® rmation if cytopathic changes in the cell culture
 Azariah and Reid. Adenovirus and non-gonococcal urethritis 549

Table 1. Summary of case histories

Genital Non-genital
Case Age Sexuality Sexual history symptoms symptoms Season

1 42 Homosexual Insertive oral sex, Dysuria, redness Sore throat Summer

anal sex with condoms
2 31 Heterosexual Insertive oral sex, vaginal Dysuria Cough, coryza, red Autumn
sex with condoms eyes, diarrhoea
3 31 Homosexual Insertive and receptive Dysuria Malaise, swollen Summer
oral sex glands
4 27 Homosexual Insertive and receptive oral Dysuria severe Gritty eyes, malaise Winter
sex, anal sex with condoms
5 40 Homosexual Insertive oral sex Dysuria, urgency, URTI, backache Summer
frequency, dribbling
6 24 Homosexual Insertive and receptive oral Dysuria Malaise Winter
sex, anal sex with condoms

Table 2. Summary of case histories

Duration of Urethral Gram stain Adenovirus cultured y Presumptive

Case Genital examination ® ndings symptoms PMNL (6100) (results of serotyping) treatment

1 Meatitis 9 days 10± 15 Urethra (15,25,29) Doxycycline

2* Penile discharge, penile shaft 11 days 5± 10 Urethra (13,19) Doxycycline,
abrasion valaciclovir
3 Meatitis, unilateral inguinal 24 days >25 Urethra (15,29) Doxycycline,
adenopathy acyclovir
4* Meatitis, unilateral inguinal 10 days (till lost to 5± 10 Urethra, conjunctiva Doxycycline,
adenopathy follow up) (untypeable) acyclovir
5* Meatitis, urethral discharge 7 days (no further <5 Urethra (untypeable) Doxycycline,
follow up) acyclovir
6* Nil abnormal 16 days <5 Urethra (untypeable) Doxycycline

*Predominance of mononuclear cells noted on Gram stain

All men tested negative for Neisseria gonorrhoeae, Chlamydia trachomatis and herpes simplex virus. Chlamydia testing was by EIA on
® rst-voided urine, gonorrhoea testing was by culture on New York City media and herpes testing was by virological culture. Routine
testing for genital mycoplasmas is not performed in this centre due to high colonization rates with these organisms and their
presence having little effect on empirical management for NGU
y Adenovirus typing done by neutralization reactions with anti-sera (ATCC), following isolation by viral culture

suggest adenovirus) or because culture for adeno-
virus was speci® cally requested due to clinical
suspicion. No comment can be made regarding
whether a particular serotype of adenovirus was
associated with genital infection in these cases. This
is because serotyping was unable to be performed
in some cases due to technical problems, or in other
cases there was cross-reaction with more than one
serotype of adenovirus (Table 2). Cross-reaction
with several serotypes is apparently a common
problem with anti-sera neutralization reactions,
although they are regarded as the gold standard
for typing of adenovirus (D Halston, Institute of
Environmental Science and Research Ltd, Kene-
puru Centre, personal communication).
Other researchers have examined the prevalence
of genital colonization of adenovirus in the past.
Harnett and Newnham3 reported the isolation of
adenovirus from 59 of 30,072 (0.2%) patients
attending a sexual health clinic during an epidemic
of adenovirus keratoconjunctivitis in Perth, Aus-
tralia. Adenovirus type 19 was isolated from 34
male urethral specimens. Thirteen (38%) of these
men had NGU not attributable to either chlamydia
or other known causes of NGU. There were no
details given of the sexual orientation or sexual
practices of these men.
Swenson et al.5 found a similar prevalence of
genital colonization with adenovirus. In their study
of 7000 male and female STD clinic attendees,
adenovirus was cultured from 20 male patients and
3 female patients, giving a prevalence of 0.33%.
Their patient group however was more selective
than in the Perth study, as all subjects were
symptomatic and were being investigated for
HSV as a possible cause of urethritis, conjunctivitis
or genital ulceration. Thirteen (65%) of these men
had NGU with no other pathogen identi® ed as the
cause of their symptoms, 12 (60%) had conjuncti-
vitis and 10 (50%) had both conjunctivitis and
urethritis. Six of the adenovirus NGU cases also
had positive conjunctival cultures. Seventeen of the
isolates were serotyped and all but 3 patients were
infected with type 37 (68%). Three of their 14
adenovirus NGU cases were men who had sex
with men; however again there was no information
given regarding the sexual practices of the study
subjects.
550 International Journal of STD & AIDS Volume 11 August 2000
Another study by Anghelscu et al.6, utilizing
indirect immun¯ uorescence, identi® ed adenoviral
antigens in several men with urethritis, however it
is dif® cult to know whether their ® ndings con-
stituted evidence of active infection or not.
These studies appear to con® rm our observation
that adenovirus colonization of the male urethra is
associated with NGU in the absence of other
pathogens. How infection occurs and what are
speci® c risk factors for genital infection with
adenovirus is not clear.
Oral sex is a known risk factor for NGU,
particularly in men who have sex with men 7,8. It
is interesting to speculate that oral sex may be a
risk factor for men to acquire urethral adenoviral
infection. However other types of intimate contact
such as kissing could be implicated, with genital
tract symptoms representing local manifestations
of a systemic infection. The higher relative pre-
valence of oro-penile sex in men who have sex with
men may mean that they have a greater risk of
adenovirus acquisition during sexual contact.
Adenovirus has been noted to be a cause of
diarrhoea in HIV-infected men 9 and this also
suggests the possibility that men who have sex
with men may have a higher risk of infection than
heterosexual men. Casual sexual contact may also
place individuals at greater risk of adenovirus
infection. However these hypotheses all remain
speculative due to limited data.
We conclude that adenovirus should be con-
sidered as a cause of NGU in particular circum-
stances. Features of the clinical presentation to
consider include symptoms of severe dysuria
associated with upper respiratory tract infection,
conjunctivitis or malaise and possibly a history of
oral insertive sex. Examination ® ndings often
reveal an obvious meatitis with an absence of
urethral discharge, and routine microscopy may
reveal an excess of mononuclear cells. There tends
to be a poor clinical response to standard therapy
for NGU or to therapy for primary genital HSV
infection. Additional treatment should consist of
supportive measures and reassurance that symp-
toms will settle.
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(Accepted 4 April 2000)