Download Chlamydial conjunctivitis: presentation and investigations

Clinical
Chlamydial conjunctivitis:
presentation and investigations
A
23-year-old female patient presented to the
emergency eye hospital with a right red sore
eye that had started 2 weeks previously. On
examination, the visual acuity was 6/6 in both eyes.
The conjunctiva was inflamed with a mild follicular
reaction. There was no enlarged pre-auricular lymph
node. An initial diagnosis was made of adenoviral
conjunctivitis, but swabs were taken, and the patient
was started on chloramphenicol drops four times a
day for 1 week to prevent secondary infection. 5 days
later the patient attended the eye casualty with worsening symptoms which included marked oedema
of the right upper eyelid and tenderness of the preauricular lymph nodes but had no fever. On examination visual acuity in the right eye was 6/9 compared
with 6/6 in the other eye. Ocular examination
revealed large follicles and large papillae of the tarsal
conjunctiva and punctuate epithelial keratitis. Additionally, extraocular movement revealed discomfort
on elevation. However, the conjunctival swabs indicated the presence of chlamydia, while other bacteriology and viral swabs were negative. The patient was
referred to the genitourinary medicine (GUM) clinic
where genital swabs were taken and the patient was
commenced on doxycycline 100 mg twice a day for
14 days. In addition, the genital swabs indicated the
presence of chlamdydia.
Chlamydial conjunctivitis typically affects sexually active teenagers and young adults and is the most
frequent infectious cause of neonatal conjunctivitis
in the UK (Denniston and Murry, 2006). The incidence of sexually transmitted disease has continued
to increase in the UK over the past decade, particularly among young people. Chlamydia has been the
most common curable sexually transmitted infection in the UK. Approximately 5–10% of sexually
active women under 24 and men between ages 20–24
may be currently infected (Baguley and Greenhouse,
2003). It is estimated that 1 in 300 patients who have
genital chlamydial disease develop adult inclusion
chlamydial conjunctivitis (Yanoff and Duker, 2004).
Between 2006–2007 there was a 7% rise in the
number of chlamydia diagnoses in GUM clinics — a
rise of 8% in men and 7% in women. Between 2008
and 2009 an estimated 16% of young people aged
15–24 in England were tested positive for chlamydia
in a community setting (outside of GUM clinics)
(National Chlamydia Screening Programme, 2009).
Abstract
Chlamydial conjunctivitis results from infection by chlamydia parasite and typically
affects sexually active teenagers and young adults. It is the most frequent
infectious cause of neonatal conjunctivitis in the UK. It is also the most common
curable sexually transmitted infection in the UK. Its clinical manifestations in the
eye involve the conjunctiva and the cornea. Untreated disease leads to a chronic
remittent course of infection, keratitis (infection to the cornea) and possibly iritis
(inflammation to the iris) and can lead to total loss of vision if left untreated.
This article will focus on the main clinical manifestation of chlamydial conjunctivitis
and its investigations. Furthermore, the article will focus on the early management
and referral of those patients who present with chlamydial conjunctivitis. Early
diagnosis and early management help to prevent ocular and sytemic complications.
By 2009 an estimated 1.5 million chlamydia tests
had been performed under the National Chlamydia
Screening Programme. Young people aged 16–24
represent 12% of the population and yet they
accounted for more than half of all new sexually
transmitted infections diagnosed in the UK in 2009.
In 2008 the 16–24 year age-group accounted for 65%
of new chlamydia diagnoses (National Chlamydia
Screening Programme, 2006).
Pathophysiology
Chlamydiae are obligate intracellular parasites
comprising three species: Chlamydia trachomatis,
Chlamydia psittaci, and Chlamydia pneumoniae. C.
trachomatis is almost exclusively a human pathogen
and includes the agents of classic trachoma. It is an
intracellular parasite but it can also duplicate extracellularly depending on the host cell. It contains its
own DNA and RNA (Kanski, 2007). The sub-group
A causes chlamydial infections, the serotypes A, B,
Ba and C cause trachoma, and serotypes D through
K produces adult inclusion conjunctivitis (Swoka et
al, 2009). Chlamydial conjunctivitis is an oclogenital
infection that results from infection by C. trachomatis. The epidemiology of the disease revolves
around sexual contact. Thereby, chlamydia can be
found in the semen of men and vaginal fluids of
women who have the infection. The infection can be
passed on from one person to another during vaginal
and/or oral sex, as well as through sharing sex toys
with an infected person. Risk factors for infection
include those aged under 25 years, a new sexual
partner or more than one sexual partner in the past
International Journal of Ophthalmic Practice • Vol 2 No 3 • June/July 2011
Mohammad Tallouzi
MSc is Advanced
Nurse Practitioner in
Ophthalmology, in the
A&E department at
Birmingham and Midland
Eye Centre. University
of Wolverhampton, and
Birmingham and Midland
Eye Hospital, Birmingham,
UK
139
Clinical
year; a new sexual partner is a greater risk factor than
having a number of partners, as is lack of consistent
use of condoms (Carder et al, 2006).
Chlamydial infection is frequently asymptomatic
in both men and women and ongoing transmission in
the community is sustained by infection going undiagnosed. Mode of transmission to the eye includes
hand to eye spread of infective genital secretions
Table 1. Investigation for chlamydia
Test
Description
Conjunctival swabs
They are used for direct immunofluorescent
staining (DFA) of the conjunctival scraping. This
technique uses the specificity of antibodies to
their antigen to target fluorescent dyes to
specific biomolecule targets within a cell, and
therefore allows visualization of the distribution of
the target molecule through the sample (Poppert
et al, 2002)
Conjunctival swabs
For chlamydia culture of conjunctiva (Kanski,
2007)
Polymerase chain reaction (PCR)
PCR is a scientific technique in molecular biology
to amplify a single or a few copies of a piece
of DNA across several orders of magnitude,
generating thousands to millions of copies of a
particular DNA sequence (Holland and Roberts,
2005)
Enzyme-linked immunosorbent Also known as an enzyme immunoassay,
assay (ELISA)
ELISA is a biochemical technique used mainly in
immunology to detect the presence of an antibody
or an antigen in a sample (Carder et al, 2006)
Giemsa staining
Giemsa staining is used in cytogenetics and for the histopathological diagnosis of chlamydia and
malaria. Basophilic intracytoplasmic epithelial
inclusion bodies are seen with Giemsa staining of
the conjunctival scrapings (Yanoff and Duker,
2004)
Serum immunoglobulin G (IgG) IgG titres to chlamydia may be obtained (Carder
et al, 2006)
A cervical swab or a vulvo vaginal swab
They are specimens of choice to test for
chlamydia and can be shown to be sensitive in
90–95% of patients (Schachter et al, 2003). If,
however, these swab examinations are not
possible then first voided urine sample would be
the alternative option. Patients should hold their
urine for at least 1 hour before providing a first
catch urine specimen (Johnson et al, 2002)
Urethral swab
The urethral swabs should be inserted 2–4cm
inside the urethra and rotated once before
removal (Johnson et al, 2002)
Urine sample
It is the most common test used at the genitourinary medicine clinics. For men the first voided urine sample is reported to be as good. Patients should hold their urine at least 1 hour before being tested (Johnson et al, 2002)
140
and even direct ejaculation into the eye (Yanoff and
Duker, 2004), although eye-to-eye contact spread has
also been reported from, for example, sharing mascara
(Rackstraw et al, 2006). Direct eye-to-eye spread may
account for about 10% of cases (Kanski, 2007).
Furthermore, chlamydia can also pass from an
infected mother to her baby during vaginal birth
and results in neonatal chlamydial conjunctivitis
(Denniston and Murry, 2006). Chlamydial neonatal
conjunctivitis is also known as ophthalmia neonatorum, which is the commonest cause of neonatal
conjunctivitis. Transferrence of chlamydial infection to the neonates increases the risk of developing
neonatal conjunctivitis by 30–40% in the new born
of an infected mother, and pneumonia by 10–20%
(Easty and Sparrow, 1999). A papillary rather
than follicular reaction is seen in neonates due to
delayed development of palpebral lymphoid tissue.
Infants present with mucopurulent discharge with
or without preseptal cellulitis. Ophthalmia neonatorum affects up to 12% of neonates in the western
world and up to 23% in developing countries. It is
potentially sight threatening and can cause systemic
complications (Yanoff and Duker, 2004).
The incubation period for chlamydial conjunctivitis is 4–12 days (Denniston and Murry, 2006).
Clinical manifestation
Ocular manifestation
To come to a conclusion regarding a chlamydial eye
infection there is a need to obtain a sample from the
eye at the eye hospital; further tests will be carried
out at the GUM clinic. Table 1 illustrates the investigations needed for diagnosis of chlamydial infection.
Ocular manifestations include:
• Subacute onset in adults is 2–3 weeks, although
the subacute onset for neonates is 4–28 day after
birth (Denniston and Murry, 2006)
• Patients present with a unilateral or bilateral (less
common) red eye with mucopurulent discharge,
marked hyperaemia, lid oedema and predominant
follicular conjunctivitis (Kanski, 2007) (Figure
1). Tender enlarged pre-auricular lymph node is
common (Yanoff and Ducker, 2004)
• Keratitis may develop during the second week
after the onset
• Corneal involvement includes superficial punctuate epithelial erosion, sub-epithelial opacities
(Denniston and Murry, 2006) and marginal or
central infiltrate may appear within 2–3 weeks
and with superior pannus being the last sign
(Kanski, 2007)
• Untreated disease leads to a chronic remittent
course of infection, keratitis and possibly iritis in
the late stage of disease (Yanoff and Ducker, 2004).
Vol 2 No 3 • June/July 2011 • International Journal of Ophthalmic Practice
Clinical
Systemic manifestation
• Systemic (common but often asymptomatic in
female and male), however, the general symptoms
can include:
• Woman — cervicitis, post-coital or intermenstrual bleeding, mucopurulent discharge, deep
dyspareunia, dysuria pelvic pain and tenderness (Horner et al, 2006; National Institute for
Health and Clinical Excellence, 2006)
• Men — urethral discharge and dysuria and
urethral discomfort.
Complications
In the absence of treatment for patients with
chlamydia, 10–40% of infected women will develop
pelvic inflammatory disease (PID) with a significant proportion of these cases being asymptomatic
or having mild, atypical symptoms (Hu et al, 2004).
However, PID can result in tubal factor infertility,
ectopic pregnancy and chronic pelvic pain (Simms
and Stephenson, 2000). Other complications include
Fitz-Hugh-Curtis syndrome (perihepatitis), epididymo-orchitis, salpingitis may result in infertility.
Kanski (2007) added that chlamydial infection in
men can cause non-specific urethritis. It may also
cause epididymitis (inflammation of the epididymis)
and act as trigger for Reiter’s syndrome and arthritis
(Westrom, 1994).
Fendler et al (2001) stated that chlamydia can
cause adult conjunctivitis, which will lead visual
impairment if not treated. This is due to infection to
the cornea and corneal opacity. Furthermore, effects
on the cornea include chronic keratitis (infection to
the cornea) and vascularization, and sub-epithelial
opacity.
Management
Chlamydial conjunctivitis is treated with topical
drops, however, the topical treatment on its own
is not enough to clear the infection, and patients
should be treated with systemic medication after
they have been investigated. The genital reservoir
should be the main focus of treatment.
Topical treatment
Topical use of antibiotics only is relatively ineffective in the treatment of ophthalmic chlamydia
conjunctivitis and does not eliminate the genital
reservoir of the disease:
• Recommended topical treatment includes erythromycin drops or tetracycline ocular ointment if
available
• Furthermore, ofloxacin and ciprofloxacin have
proved to be effective against C. trachomatis as
well as the possibly associated infection Neisseria
Figure 1. Chlamydial conjunctivitis showing
inflamed conjunctiva (top) and upper palpebral
conjunctiva with follicles (bottom).
gonorrhoeae. It can be applied four times daily for
a maximum of 10 days (British National Formulary, 2010)
• Although chloramphenicol has a relatively broad
spectrum of action against most gram-positive and
gram-negative bacteria, it is not effective against C.
trachomatis (Easty and Sparrow, 1999).
Systemic treatment
Systemic therapy should not be started prior to genitourinary investigations. The presence of chlamydial
conjunctivitis does not always indicate the presence
of genital chlamydial infection since chlamydial
conjunctivitis may be transferred by routes other
than the genitourinary route, such as the sharing of
eye make up. Therefore, it is important to confirm
the presence of chlamydial infection in both the eye
and the genital area. This will ensure the correct
treatment is used for the right infection. Furthermore, sampling patients might indicate the presence of other organisms which might require alternative treatment. The result of the specimen taken
will confirm not only the organism that is to be
International Journal of Ophthalmic Practice • Vol 2 No 3 • June/July 2011
141
Clinical
treated, but also the duration of treatment required.
The following highlights the most common regimen
of systemic medication used in the treatment of
chlamydial infection.
Recommended regimens: first line treatment
• Doxycycline 100 mg twice daily (bd) for 7 days
(contraindicated in pregnancy) or
• Azithromycin 1 g orally in a single dose (contraindicated when there is loose stools, diarrhoea,
abdominal pain, headache or unexplained rash).
Alternative regimens
There are alternative regimens that can be used if
either of the above treatments are contraindicated:
• Erythromycin 500 mg four times a day for 7 days or
• Erythromycin 500 mg bd for 10–14 days or
• Amoxicillin 500 mg three times a day for 7 days or
• Ofloxacin 200 mg bd or 400 mg once a day for 7
days (Horner et al, 2006).
Treatment guidelines
Due to a higher number of positive chlamydia test
results following treatment during pregnancy, attributed to either less efficacious treatment regimen, non
compliance or re-infection, it is recommended that
pregnant woman must have a test of cure 5 weeks
after completing therapy, 6 weeks later if given
azithromycin (Brocklehurst and Rooney, 2000).
Doxycycline and ofloxacin are contraindicated
in pregnancy and breastfeeding, as they have been
shown to cause arthropathy and hypoplasia (British
National Formulary, 2010).
Azithromycin is probably less than 95% effective
(Brocklehurst and Rooney, 2000). Single oral dose
of azithromycin has proved to be a more effective
and convenient treatment for sexually transmitted
infections in women in a resource-poor environment
(Rustomjee et al, 2002). Azithromycin is a subclass
of the macrolide antibiotics family. It works by
blocking the actions of certain proteins that bacteria
need in order to thrive (Rang et al, 2007). Without the
proteins, the bacteria are prevented from growing,
replicating and multiplying. With the spread of the
infection curbed, the remaining bacteria are killed
off by the body’s immune system or die of their
own accord. Azithromycin has been most effective
against isolates of many different micro-organisms
(Bennet and Brown, 2003).
WHO guidelines recommend 1 g of azithromycin
stat to treat C. trachomatis in pregnancy (British
Association of Sexual Health and HIV, 2006); the
British National Formulary recommends its use in
pregnancy and lactation only if no alternative is
available.
142
Erythromycin has a significant side-effect profile and
is less than 95% effective against chlamydial infection.
There are no trials of the effect of erythromycin 500
mg twice a day on chlamydial infection lasting 14 days
(Kacmar et al, 2001). It can cause colitis, and reversible hearing loss after large dose has been reported
(Rang et al, 2007). Cholestatic jaundice, pancreatitis,
cardiac effects including chest pain and arrhythmias,
myasthenia like syndrome, Steven Johnson syndrome
and toxic epidermal necrolysis have also been reported
(British National Formulary, 2010)
Tetracyclines should be avoided in children
younger than 7 years and in women who are pregnant or breastfeeding. It has been reported to have
an effect on the skeletal development, and maternal
hepatotoxicity, and discolouration of teeth in infants
is usually prevented by chelation with calcium in
milk (British National Formulary, 2010).
Patients should be advised to avoid sexual intercourse (including oral sex) until they and their
partner(s) have completed treatment.
Furthermore partners should be notified and
referred to the GUM clinic. Information should be
provided for both the person with chlamydia and
their partners as this reduces the rates of persistent
or recurrent infection (National Institute for Health
and Clinical Excellence, 2007).
Part of the management plan for all patients with
chlamydial conjunctivitis is psychological support,
health advice and education. Patients will express
anxiety especially after receiving a positive test
result regardless of whether they anticipated it. This
may be due to the fear of informing sexual partners
of being unfaithful, the risk of infertility and the
possibility of having other undetected infections.
Furthermore, women’s concern about being stigmatized for contracting a chlamydial infection, affects
how they feel about themselves and how they think
others perceive them (Mills et al, 2005).
Role of the ophthalmic nurse
Ophthalmic nurse practitioners play a role in
providing teaching and advice about sexually transmitted infections and should help to increase the
awareness and acceptability of chlamydial eye infection. They should also provide information on how
to avoid the sight-threatening complications associated with it. Nurses should always stress the importance of instilling the antibacterial eye drops and
artificial tear drops as prescribed and the importance
of attending the eye clinic for further follow-up care
and treatment as needed. All patients will be advised
to come back if there is any deterioration in the visual
acuity or if the eyes have become more painful.
Also, patients will be advised to avoid make up and
Vol 2 No 3 • June/July 2011 • International Journal of Ophthalmic Practice
Clinical
encouraged to use artificial tear drops regularly to
lubricate the eye and make it feel more comfortable.
In addition, the ophthalmic nurse practitioners’
role is to arrange the referral to the GUM clinic
where further investigations will be carried out and
where treatment will be issued. Nurse practitioners
at the GUM clinic will provide more advice about
screening of the chlamydial infection and the need
to test the partner as well. All attendees of GUM
clinics receive information and advice from health
advisors including information about future reproductive health ability and future sexual relationships (Dixon-Woods et al, 2001). Patients will be
asked to attend the clinic again to have their urine
tested for chlamydia (men and women) and a vaginal
swab (women) after treatment has finished in order
to make sure the infection has cleared up.
Clinical scenario outcome
The patient in this scenario was treated with ofloxacin
eye drops four times a day for a week and given celluvisc eye drops (artificial tears) four times a day, and
when needed, for a month. She was also treated by
the GUM clinic with doxycycline 100 mg twice a day
for 14 days. Following treatment a vaginal swab and
a urine sample were tested, and these were negative.
References
Baguley S, Greenhouse P
(2003) Non genital manifestation of chlamydial
tracomatis. Clin Med3(3):
206–8
Bennet P, Brown M (2003)
Clinical Pharmacology.
9th edn. Churchill Livingstone, Elsevier Science
Limited
British National Formulary
60 (2010) British National
Formulary. 58th ed.
British Medical Association and Royal Pharmaceutical Society of Great
Britain, London
Brocklehurst P, Rooney G
(2000) Interventions for
treating genital chlamydia
trachomatis infection
in pregnancy. Cochrane
Database of Systematic
Reviews (2)
Carder C, Mercey D, Benn P
(2006) Chlamydia trachomatis. Sexually Transmitted Infections 82(l 4):
10–2
Denniston A, Murry P
(2006) Oxford Handbook
of ophthalmology 1st edn.
Oxford University Press,
Oxford
Dixon-Woods M, Stokes
T, Young B, Phelps K,
Windridge K, Shukla
R (2001) Choosing and
using services for sexual
health: a qualitative
study of women’s views.
Sex Transm Infect 77(5):
335–9
Easty DL, Sparrow JM
(1999) Oxford textbook of
ophthalmology volume 1
1st edn. Oxford University Press, Oxford
Fendler C, Laitko S,
Sörensen H et al (2001)
Frequency of triggering
bacteria in patients with
reactive arthritis and
undifferentiated oligoarthritis and the relative
importance of the tests
used for diagnosis. Ann
Rheum Dis 60(1): 337–43
Holland J, Roberts J (2005)
Chlamydia trachomatis
PCR positivity and
inflammatory changes
on cervical cytology.
Sex Transm Infect 81(1):
360–1
Horner PJ, Boag F, Radcliffe
R et al (2006) National
guideline for the management of genital tract
infection with Chlamydia
trachomatis. British Association for Sexual Health
and HIV
Hu D, Hook EW, Goldie
SJ (2004) Screening for
Chlamydia trachomatis in
Women 15 to 29 Years of
Age: A Cost-Effectiveness
Analysis. Ann Intern Med
141(7): 501–13
Johnson RE, Newhall
WJ, Papp JR, Knapp
Key points
• Know how to recognize and investigate chlamydial conjunctivitis.
• Understand the routine management of chlamydial infection and the referral
process for those patients.
Ophthalmology • Chlamydial conjunctivitis • A&E
In addition, the patient attended the eye clinic 1
month later and the eye looked much better. There
was some tear film disturbance and superficial
epithelial staining so she was kept on celluvisc 1%
6–8 times a day and some lacrilube gel at night for a
month to lubricate the eye.
Conclusion
Chlamydia is the most common curable sexually
transmitted infection in the UK. Chlamydial conjunctivitis is one of the main sequeli of chlamydial infection. Early management of chlamydial infection helps
prevent damage to the vision for infected patients as
well as preventing other systemic complications.
Therefore, early referral to an ophthalmologist is very
important for those patients presenting with unilatIJOP
eral red eye for a period of over 2–3 weeks. Conflict of interest: none.
JS, Black CM, Gift TL
(2002) Screening tests
to detect Chlamydia
trachomatis and Neisseria
gonorrhoeae infections.
Morbidity & Mortality
Weekly Report. Recommendations & Reports
51(15): 1–38
Kacmar J, Cheh E, Montagno
A, Peipert JF (2001)
A randomized trial of
azithromycin versus
amoxicillin for the
treatment of Chlamydia
trachomatis in pregnancy.
Infect Dis Obstet Gynecol
9(4): 197–202
Kanski J (2007) Clinical
ophthalmology – A
systematic Approach 6th
edn. Butterworth-Heinemann. Elsevier Science.
Millsa,
Mills N, White G, Graham
A, Campbell R (2005)
Population screening for
Chlamydia trachomatis
infection in the UK: a
qualitative study of the
experiences of those
screened. Oxford Journal
23(5): 550–7.
National Chlamydia
Screening Programme
(2006) New Frontiers;
Annual Report of the
National Chlamydia
Screening
National Chlamydia
Screening Programme
International Journal of Ophthalmic Practice • Vol 2 No 3 • June/July 2011
(2009a) What is the
NCSP? The National
Chlamydia Screening
Programme
National Institute for Health
and Clinical Excellence
(2007) One to one interventions to reduce the
transmission of sexually
transmitted infections
(STIs) including HIV,
and to reduce the rate
of under 18 conceptions, especially among
vulnerable and at risk
groups. National Institute
for Health and Clinical
Excellence
Poppert S, Essig A, MarreR,
Wagner, Horn H (2002)
Detection and Differentiation of Chlamydiae
by Fluorescence In Situ
Hybridization. Applied
and Environmental
Microbiology 68(8):
4081–9
Rackstraw S, Viswalingam
ND, Goh BT (2006) Can
chlamydial conjunctivitis
result from direct ejaculation into the eye? Int J
STD AIDS 17(9): 639–41
Rang H, Dale M, Ritter J,
Flower R (2007) Rang and
Dale’s Pharmacology 6th
edn. Churchill Livingstone, Elsevier Science
Limited
Rustomjee R, Kharsany
AB, Connolly CA,
Karim SS (2002) A
randomized controlled
trial of Azithromycin
versus Doxycycline/
Ciprofloxacin for the
syndromic management
of sexually transmitted
infections in a resourcepoor setting. Journal of
Antimicrobial Chemotherapy 49(5): 875–8
Schachter J, McCormack
WM, Chernesky MA et al
(2003) Vaginal swabs are
appropriate specimens for
diagnosis of genital tract
infection with Chlamydia
trachomatis. J Clin Microbiol 41(8): 3784–9
Simms I, Stephenson JM
(2000) Pelvic inflammatory disease epidemiology: what do we know
and what do we need to
know? Sex Transm Infect
176(2): 80–7
Swoka JW, Gurwood AS
Kabat AG (2009) The
Handbook of Ocular
Disease Management 11th
edn. Review of optometry.
Jobson Publication
Westrom LV (1994) Sexually
transmitted diseases and
infertility. Sex Transm Dis
21(2): 32–7
Yanoff M, Duker J (2004)
Ophthalmology 3rd edn,
Mosby Elsevier
143