VAGINAL INFECTIONS
Trichomoniasis
David Lewis
Abstract
Trichomoniasis is caused by the protozoan, Trichomonas vaginalis. It is a
common sexually transmitted infection, particularly among women, in
whom it causes a vaginal discharge and vulvitis. Urethral symptoms in
men are usually mild and transient. It has been associated with adverse
pregnancy outcome and enhances HIV transmission. Molecular tests
have shown the inferiority of standard wet film microscopy and culture
methods. Increased use of molecular and rapid point-of-care tests in
high prevalence populations will enhance case finding and treatment.
Keywords Diagnostics; HIV; metronidazole; pathogenesis; pregnancy;
resistance; trichomoniasis
Introduction
Trichomoniasis is a common sexually transmitted infection (STI)
caused by infection with Trichomonas vaginalis.1 T. vaginalis is
classically visualized as a flagellated trophozoite with five
flagella that are responsible for the protozoan’s characteristic
motility (Figure 1).2 The organism may exist also in several other
cellular forms including the amoeboid form, which occurs when
trophozoites come into contact with host epithelial cells
(Figure 1), and the pseudocyst form, which can be experimen-
tally induced upon exposure of trophozoites to stressors such as
cold temperature.2 The role of pseudocysts in causing human
disease remains unclear but they have been shown to persist and
cause vaginal infection in a mouse model of vaginal
trichomoniasis.3
Epidemiology and transmission
In 2008, the WHO estimated that the worldwide incidence of
trichomoniasis was just over 276 million cases per year.4
Although most cases occur in resource-poor countries, there
are approximately 3 million cases among women of reproductive
age in the USA each year.5 In 2011, approximately 6200 new
cases of trichomoniasis were identified in genitourinary medicine
clinics in England.6 Most of these cases (93%) were diagnosed in
women while 7% occurred in heterosexual men.
The importance of sexual contact in the transmission of
trichomoniasis is well established. Although T. vaginalis can
survive in body fluids and on moist surfaces, there are very few
well-documented cases of non-venereal transmission. Tricho-
moniasis may also be transmitted perinatally from infected
mothers to female babies.7 Predisposing factors for sexual
transmission include non-use of condoms or oral contraceptives,
smoking and low socioeconomic class.
David Lewis FRCP(UK) PhD is Head of the Centre for HIV and STIs at the
National Institute for Communicable Diseases (NHLS), Johannesburg,
South Africa. Competing interests: none declared.
MEDICINE 42:7
What’s new?
C Molecular diagnostics and rapid point-of-care tests for Tricho-
monas vaginalis are much improved and will assist with
screening for trichomoniasis, particularly among men and
asymptomatic women
C Despite widespread use of metronidazole, there is no evidence
for a rise in the prevalence of metronidazole-resistant
trichomoniasis
C The T. vaginalis genome sequence was published in 2007 and
has identified several unique characteristics of the organism
C Recent research on T. vaginalis pathogenicity has focused on (i)
how the organism interacts with host cells and the vaginal
microbiota, and (ii) what factors regulate the transformation of
the parasite from a flagellated trophozoite to the amoeboid
form
It has been shown that trichomoniasis, like many other STIs,
can act as a co-factor for HIV transmission.8 This is thought to
occur through increased local accumulation of HIV-infected or
HIV-susceptible immune cells.
Pathogenesis
Intravaginal challenge of pre-oestrogenized mice with T. vagi-
nalis has been used to study the pathogenesis of trichomoniasis,
which is likely to be multifactorial, involving a complex interplay
between immune evasion, cyto-adherence and environmental
regulation of gene expression.9 Important attributes for virulence
appear to be variation in the expression of surface antigens,
secretion of extracellular proteinases, haemolytic activity, cell
ecell adhesion, and interactions with other members of the
vaginal microflora.2
Figure 1 This scanning electron micrograph shows T. vaginalis (green)
interacting with human vaginal epithelial cells (red). Two distinct mor-
phologies are indicated: (a) the rounded, pear-shaped free swimming
form, (b) the adherent amoeboid-shaped form. (Courtesy of Marlene
Benchimol and Victor do Valle Midlej, Santa Ursula University, Rio de
Janeiro, Brazil).
369 Ó 2014 Elsevier Ltd. All rights reserved.
 VAGINAL INFECTIONS

Clinical features
Women: T. vaginalis is usually isolated from the vagina; the
urethra and Skene’s glands are also commonly infected.10
Asymptomatic infections are well documented, occurring in 10
e50% of women attending STI clinics. Symptomatic women
present with vaginitis and vulvitis (Figures 2 and 3). The clas-
sical vaginal discharge of trichomoniasis is green, frothy, itchy
and malodorous, though in clinical practice the discharge is often
grey and non-itchy (Figure 2). The vaginal walls and cervix may
be erythematous, and a ‘strawberry cervix’ is seen on speculum
examination in about 2% of cases (Figure 2).10 Women may also
complain of dyspareunia, dysuria and urinary frequency. The
symptoms of trichomoniasis may worsen during or shortly after
menstruation.
Associations include: Figure 3 Vulvitis due to chronic trichomoniasis.
 adverse pregnancy outcome
 increased incidence of post-hysterectomy infection Diagnosis
 infertility
Microscopic examination of saline wet mounts taken from the
 increased incidence of cervical intraepithelial neoplasia
posterior vaginal fornix or urethra is the conventional method
and cervical carcinoma.
used to demonstrate the presence of motile T. vaginalis.12
However, the sensitivity of this technique is at best only about
Men: T. vaginalis may infect the urethra, the epididymides and
70e80% compared with broth culture methods.9,13 The main
the prostate gland.11 Most men remain asymptomatic. Those
disadvantage of in vitro culture methods is the need to incubate
with symptoms usually present with non-specific urethritis
samples for several days before the organism can be detected. In
(NSU). Rarely, T. vaginalis causes clinically apparent balanitis,
addition, many clinicians do not have access to culture facilities.
epididymitis or prostatitis.
Various staining techniques (e.g. acridine orange stain) have
Associations include:
been used in an attempt to improve the diagnostic sensitivity of
 impaired sperm mobility
microscopy.13 Trichomonads may be seen in cervical smears
 reduced sperm viability.
stained with Papanicolaou’s stain, but this is not regarded as a
reliable diagnostic method. Newer monoclonal antibody-based
rapid point-of-care tests and nucleic acid amplification tests
(NAATs) have been developed to detect T. vaginalis in genital
specimens, but these are not routinely used in most clinical
settings.12 Point-of-care tests for T. vaginalis offer an opportunity
to screen high-prevalence populations in non-clinical settings
and could be of use in screening pregnant women in resource-
poor settings in order to enable same-day treatment to avoid
pregnancy complications. NAATs for the detection of T. vaginalis
may have diagnostic sensitivities approaching 100% and are the
only method of value in the investigation of men.

Differential diagnosis
In women, differential diagnoses include other causes of vaginal
discharge; namely, bacterial vaginosis and candidiasis. In men,
the other causes of NSU must be excluded.

Management
Until the discovery of metronidazole in 1959, topical vaginal
preparations provided symptomatic relief but seldom cured
trichomoniasis in women. A problem with all topical treatments
is lack of penetration of the urethra and Skene’s glands, which
may act as a reservoir for the organisms. Since the 1960s,
metronidazole has been the mainstay of anti-trichomonal ther-
apy. Other nitroimidazoles (e.g. tinidazole) have also been suc-
cessful. UK national guidelines recommend treatment with oral
Figure 2 Frothy vaginal discharge of trichomoniasis with a strawberry metronidazole, 2 g as a single dose or given as 400e500 mg
cervix. 12-hourly for 5e7 days.14 The single-dose regimen achieves

MEDICINE 42:7 370 Ó 2014 Elsevier Ltd. All rights reserved.

 VAGINAL INFECTIONS
better patient compliance and has fewer adverse effects, but may
be slightly less effective. Meta-analyses indicate that there is no
evidence of metronidazole-induced teratogenicity in women
treated with metronidazole during the first trimester of
pregnancy.14
Cure rates with metronidazole are high when the patient
complies with treatment and is not re-infected by an untreated
partner. Treatment failures that are not a consequence of poor
compliance or re-infection may result from resistance of T. vag-
inalis to metronidazole. The prevalence of metronidazole-
resistant T. vaginalis strains remains low. Within the UK, a test
of cure one week after finishing therapy is therefore not recom-
mended unless the patient continues to have symptoms or if
symptoms recur.14 However, significant numbers of early
repeated infections after oral administration of a single 2 g dose,
irrespective of HIV status, have been reported in the USA.15 This
suggests that re-screening women following single dose therapy
should be considered in high prevalence settings.
Management of resistant cases is difficult.16 As an initial
approach, intravenous or higher-dose oral metronidazole are
prescribed for extended periods. This may be combined
with metronidazole vaginal pessaries. Alternative therapeutic
approaches include tinidazole, nonoxynol-9 vaginal pessaries,
clotrimazole pessaries, acetarsol pessaries, vaginal paromomycin
preparations, and a combination of broad-spectrum antibiotics
and metronidazole.16
Screening for other STIs should be offered to all patients with
trichomoniasis.
Partners e sexual partners from the preceding four weeks
should be screened and given empirical treatment.
Prevention
Repeated infection with T. vaginalis does not induce protective
immunity in humans, despite detection of anti-trichomonal
antibodies in the serum and vaginal fluids of such patients.
The only vaccine evaluated to date is Solco Trichovac, which is
prepared from an inactivated Lactobacillus acidophilus strain.
The results of clinical trials have been inconclusive. A
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Practice points
C Patients with trichomoniasis should be offered screening for other
STIs, and their sexual partners should be screened and treated
C Men are often asymptomatic, and diagnosis of trichomoniasis is
difficult
C When treatment fails, exclude poor compliance and re-infection
before assuming metronidazole resistance
C Discuss treatment options for metronidazole-resistant trichomo-
niasis with an experienced colleague
371 Ó 2014 Elsevier Ltd. All rights reserved.