Variants highlights the various ocular manifestations of

Variants of Ocular Melioidosis in
Hospital Selayang: A Case Series

 

Jeyarine Royan1,
Khairy Shamel Sonny Teo1, Hanizasurana Hashim2

We Will Write a Custom Essay Specifically
For You For Only $13.90/page!


order now

 

1 Department of
Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kubang
Kerian, Kelantan, Malaysia

 

2 Hospital
Selayang, Selangor, Malaysia

 

 

ABSTRACT

TITLE:

Variants of Ocular Melioidosis in
Hospital Selayang : A Case Series

 

BACKGROUND

Melioidosis is multi-system
infectious disease which is endemic in Malaysia. Melioidosis causing localized
ocular infection has rarely been reported. This study highlights the various ocular
manifestations of melioidosis in patients with positive serology for Burkholderia
pseudomallei in Hospital Selayang

 

METHOD

This was a retrospective case
series involving patients with ocular melioidosis diagnosed in Hospital
Selayang from 2013 to 2016

 

RESULTS

There were three patients in
this series. All were immunocompetent, with no systemic evidence of infection.

One case had unilateral disease; the other 2 were bilateral, with common
presenting symptoms of pain, redness and blurring of vision.

All patients had positive
serology for Burkholderia pseudomallei and were treated with intravenous ceftazidime
and either oral sulfamethoxazole-trimethoprim (Bactrim) or oral cefuroxime for
a minimum of 2 months.

 

 

CONCLUSIONS

Melioidosis can manifest as an ocular infection in both the anterior and
posterior segments of the eye. The diagnosis is clinical in nature and early empirical
therapy should be commenced whilst awaiting confirmatory serology results.

 

Keywords:
Ocular; infection; Melioidosis; Burkholderia pseudomallei

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

INTRODUCTION

 

Melioidosis is an infectious
disease caused by the aerobic bacteria Burkholderia pseudomallei. It is endemic in tropical regions like South East
Asia and Northern Australia and can result in multi-system infection. The
manifestations of the infection are extremely vast, ranging from ocular
infections to soft tissue infections, septicemia, pneumonia, osteomyelitis and
central nervous system infection.

Burkholderia pseudomallei
is the causative agent in a host of multi system infections.

 

We report a case series of three
patients who were treated for ocular Melioidosis based on clinical features and
positive serology tests for Burkholderia pseudomallei.

 

METHODS

This was a restrospective case
series of 3 patients with ocular Melioidosis who presented to Hospital Selayang
from 2013-2016.

The demographic details (age and
gender), case notes, anterior segment and fundus photographs, blood
investigations and ocular investigations were analyzed. All patients had
serological testing for Burkholderia pseudomallei (IGM levels) which was sent
to Institiute of Medical Research, Kuala Lumpur for analysis.

 

 

 

 

 

RESULTS

 

CASE 1

 

 A healthy
33-year-old lady presented with a 5-day history of right eye redness and pain.

There were no systemic complaints. She denied any risk factors for Melioidosis
such as diabetes mellitus, open wounds and environmental or occupational
exposure to soil and water.

 

On examination, VA OD was 6/24 unaided, OS 6/9.

Intraocular pressures in both eyes were normal. The right anterior segment had
diffuse injection and superotemporal scleral tenderness. The anterior chamber
was deep, with plasmoid,fibrinous aqueous, cellular activity of 4+and a streak
of hypopyon. (Figure 1). Fundus examination revealed a normal optic disc, but
details of the fundus in the RE were obscured by the anterior media opacity. On
B scan ultrasonography, there were no vitreous opacities or loculations and
T-sign was absent. The left eye findings were unremarkable. Diagnosis of right
eye severe anterior sclerouveitis was made.She was commenced on Gutt
dexamethasone hourly, Gutt homatropine 8 hourly and T.ibuprofen 400mg 12
hourly. Blood investigations revealed mild leukocytosis. As the hypopyon level
appeared to be rising, she was commenced on intravenous ceftazidime 1gm 12
hourly, hourly Gutt moxifloxacin 0.5% and given intracameral moxifloxacin.

 

Meanwhile the serology for
Burkholderia pseudomallei returned positive. Blood and aqueous fluid
cultures were negative. After 4 days of IV Ceftazidime, the VA OD improved to
6/12. The cellular activity had reduced to 1+ and the hypopyon resolved.

 

She was discharged with oral bactrim
(trimethoprin + sulfamethoxazole)960 mg 12hourly for 8 weeks. Final VA OD
improved 6/9 unaided, with normal ocular findings.

 

 

CASE 2

 

A healthy 21-year-old lady with no
past medical history was referred for a 4-month history of redness and pain in
the left eye, which was initially treated as anterior uveitis. Her blood
investigations were positive for toxoplasma IgM, so she had been treated with
oral clindamycin and prednisolone. She was working as a traditional healer,
which involved intermittent exposure to blood and body fluids.

 

On examination VA OD was 6/9, OS
was HM. The right eye was normal. Intraocular pressures were also normal. Left
eye examination revealed keratic precipitates, cellular activity of 1+,
posterior synechiae and posterior subcapsular cataract. Fundus examination OS
revealed a swollen optic disc, oedematous macula with a partial macular star
and vitritis. (Figure 2)

 

Optical coherence
topography demonstrated intraretinal and subretinal fluid OS.

 

She was commenced on oral doxycycline
100mg 12 hourly as well as Gutt dexamethasone 4hourly and G homatropine 8
hourly. Initially there was improvement; however, a few weeks later her vision
deteriorated further and there was increase of cellular activity and vitritis.

She was empirically started on IV ceftazidime 1gm 12 hourly which was given for
6 days and Gutt moxifloxacin 4hourly.Systemic prednisolone was started to
hasten the resolution of exudation.

Repeat investigations including
infective screening, blood and urine cultures were negative. At this juncture,
the serology for Burkholderia pseudomallei returned positive.

 

As her condition improved, the
steroids were tapered off. She then completed two months of Oral bactrim (trimethoprin
+ sulfamethoxazole) 960mg 12 hourly. Repeated serology of Burkholderia pseudomallei was negative.She was
scheduled for LE synechiolysis with cataract extraction and IOL insertion.

 

On her pre-operative assessment 2
months later, both eyes had cells of 3+.VA was 6/12 OD and CF 1ft OS.The RE
fundus examination revealed a hyperemic optic disc and macula striation; however,
there was no vitritis or retinitis. The repeated Burkholderia pseudomallei
serology was positive with a titre of 1:160. 
IV ceftazidime 1gm 12 hourly was given for 14 days, followed by oral bactrim
for 8 weeks and tapering doses of oral prednisolone.

 

During follow up, whilst still on bactrim
(with history of poor compliance), the VA was 6/12 OD and HM OS. There was
anterior chamber reaction of 3+ bilaterally and a hyperemic disc OD.  Fundus fluorescein angiogram OD revealed
leakage from the disc, perifoveal vasculitis and small vessel vasculitis in all
quadrants, but no areas of capillary non-perfusion.  Repeated Burkholderia serology now was
negative, however, she was noted to have positive Bartonella hensei serology.

She was started on Oral doxycycline 100mg 12 hourly. She subsequently defaulted
follow up.

 

 

 

 

CASE 3

A healthy 10-year-old boy presented
with a 2-week history of bilateral eye redness, tearing and generalized
blurring of vision, which was preceded by fever that resolved with oral
antibiotics and anti-pyretics. He had history of camping 2 months ago. On
examination, VA OD was 6/18, OS 6/24. Both eyes had conjunctival injection,
endothelial dusting, cellular reaction of 3+ and anterior vitreous cells of 1+.

Bilateral fundus examination revealed swollen discs with periphlebitis and
sheathing in all 4 quadrants with macula striation. (Figure 3). There was no
obvious retinitis or choroiditis. He was commenced on Gutt dexamethasone 2hourly
and Gutt homatropine 8hourly for BE whilst awaiting his blood investigation
results. On review 2 days later, his symptoms remained the same, as did the
ocular findings. Baseline blood investigations and work up for Tuberculosis
were normal. He was admitted for BE endogenous endophthalmitis and started on
IV ceftazidime 25mg/kg 8hourly and Gutt moxifloxacin 2hourly BE. After
completion of one week of IV ceftazidime, his symptoms improved and VA BE
improved to 6/9, with cellular reaction of 1+, with resolving periphlebitis and
optic disc swelling. Burkholderia pseudomallei serology returned positive. He
was discharged with oral cefuroxime 250mg 12 hourly after consulting with the
pediatrician. 1 month later his VA had improved to 6/6 BE with no cellular
activity and resolution of vasculitis in both eyes. He completed 8 weeks of
oral cefuroxime and repeat Burkholderia serology was negative. His final VA was
6/6 BE with normal ocular findings.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 1 (Case 1)

Anterior
segment photograph showing conjunctival hyperemia with hypopyon OD

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 2 (Case 2)

Fundus photo OS a showing swollen
optic disc, macular oedema, partial macular star and vitritis

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 3 (Case 3)

Fundus photo OS showing periphlebitis and
optic disc swelling

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

DISCUSSION

 

Burkholderia pseudomallei
is the causative agent in a host of multi-system infections. The organism is

 

endemic in southeast Asia and tropical Australia.(1) It is a motile, non- spore
forming, aerobic gram

 

negative bacillus which is mostly found in soil and water.(1) Infections secondary to the
organism

 

occur following exposure via inhalation, ingestion or skin
inoculation to contaminated soil or water.(2)

 

Transmission may rarely occur via contact with infected
blood or body fluids in a laboratory setting.(3)

 

There are certain predisposing factors for acquiring melioidosis,
the commonest in the

 

Malaysian setting being diabetes mellitus.(4-6).Other
risk factors include environmental and

 

occupational exposure to wet soil and water, chronic renal disease,
tuberculosis and

immunosuppressed states.

 

Melioidosis can present as a localized infection, bacteremia
or disseminated

 

infection. It can also present as a subclinical infection;
however, the incubation period of the disease is

 

 not well defined.(1)
Melioidosis has even been found to occur without any obvious focus of infection,

 

and the opportunistic nature of the organism results in the infection
occurring in healthy

 

immunocompetent individuals without predisposing factors. (7)

 

 

The wide
spectrum of clinical symptoms, signs and infection sites has earned Melioidosis
the title of

 

 the “great mimicker”. (1, 3, 5) This description has
been used to describe the multi-system

 

involvement
of Melioidosis, however the ocular manifestations of this infection have rarely
been

 

reported
in the literature. Our case series demonstrates that just like other
Melioidosis infections with

 

multi
system involvement, isolated ocular Melioidosis can present with various manifestations.

The

 

wide
spectrum of presentations and lack of clinical evidence of systemic infection
renders it a complex

 

clinical
problem and poses a diagnostic challenge.

 

 

This case series involved 3 patients
with no systemic evidence of Melioidosis who presented with ocular symptoms
attributed to Burkholderia pseudomallei, as evidenced by the positive serology
results and good response to treatment with intravenous ceftazidime. All the
patients were young and healthy with no history of diabetes mellitus or
immunosuppression. Two out of the 3 patients had risk factors that may have
contributed to the ocular infection (exposure to blood and history of camping
thus having environmental exposure to soil and water), athough there was no
history of open wounds on the skin.

 

In case 1, the
ocular findings were confined to the anterior segment, however in cases 2 &
3, there was both anterior and posterior segment involvement, with intense
inflammation. Ocular fluid (aqueous) was sent for culture in case 1, but did
not yield any positive result. This could be due to the scarce volume of fluid available
for sampling, resulting in a low yield.

 

The prevailing
gold standard of confirming a clinical diagnosis of Melioidosis is by isolating
Burkholderia pseudomallei from clinical specimens.(8, 9)
Serological testing is beneficial in endemic areas as it can be used as a
preliminary test whilst awaiting positive culture reports which may be time
consuming and cause a delay in treatment, however the sensitivity rates are
lower than cultures. Examples of serological tests for Melioidosis include indirect
hemagglutination assay (IHA), IgM and IgG Enzyme-linked immunosorbent assay
(ELISA) and Indirect immunofluorescent test (IFAT).(9)
The latter 2 tests were the serological tests used in our case series.

 

In all 3 cases, empirical treatment
was commenced whilst awaiting confirmatory serological tests for Burkholderia
pseudomallei. Cases 1 & 3 showed good response to treatment with good
visual outcomes and no sequelae; Case 2 however defaulted treatment and follow
up. The patient in case 2 sought treatment late, hence further diagnosis and
treatment were also delayed.

 

The recommended treatment for severe
septicemic Melioidosis involves a combination of high dose intravenous ceftazidime
and trimethoprim-sulphamethoxazole for up to 2 to 4 weeks as the immediate form
of therapy , followed by an eradication phase with trimethoprim-sulphamethoxazole
or oral doxycycline for 12-20 weeks to prevent recurrences.(10)
There are no specific treatment guidelines for localized ocular Melioidosis.

The patients in this case series showed a good response with the standard
antimicrobial regimes used in combination with topical steroids, as there was
reduction of inflammation and clinical signs after a few days of intravenous
ceftazidime in all 3 cases.

 

The commonest form of presentation
of ocular Melioidosis is severe uveitis (which was seen in all 3 cases) and the
cases were isolated, without any obvious clues of risks or systemic findings.

As ocular Melioidosis can occur in healthy individuals in endemic areas, it is
imperative to include Melioidosis serology as a routine blood investigation, as
a delay in diagnosis can result in poor visual outcomes, as seen in case 2.

 

Melioidosis is known in Malaysia
for the wide range of systemic infections and it remains a difficult infection
to diagnose given its many presentations. As with other forms of Melioidosis,
the ocular variant which is localized to the eye may present with various forms
of uveitis in a healthy individual. Early treatment can result in complete
resolution of infection with no sequelae.

 

Conclusion

Ocular Melioidosis is commonly
underdiagnosed in endemic areas and should be suspected in any severe form of
uveitis, especially those which do not respond to the initial treatment. Empircal
therapy can be initiated whilst awaiting confirmatory serological testing.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

REFERENCES