Variants of Ocular Melioidosis inHospital Selayang: A Case Series Jeyarine Royan1,Khairy Shamel Sonny Teo1, Hanizasurana Hashim2 1 Department ofOphthalmology, School of Medical Sciences, Universiti Sains Malaysia, KubangKerian, Kelantan, Malaysia 2 HospitalSelayang, Selangor, Malaysia  ABSTRACTTITLE:Variants of Ocular Melioidosis inHospital Selayang : A Case Series BACKGROUNDMelioidosis is multi-systeminfectious disease which is endemic in Malaysia.

Melioidosis causing localizedocular infection has rarely been reported. This study highlights the various ocularmanifestations of melioidosis in patients with positive serology for Burkholderiapseudomallei in Hospital Selayang METHODThis was a retrospective caseseries involving patients with ocular melioidosis diagnosed in HospitalSelayang from 2013 to 2016 RESULTSThere were three patients inthis series. All were immunocompetent, with no systemic evidence of infection.One case had unilateral disease; the other 2 were bilateral, with commonpresenting symptoms of pain, redness and blurring of vision.All patients had positiveserology for Burkholderia pseudomallei and were treated with intravenous ceftazidimeand either oral sulfamethoxazole-trimethoprim (Bactrim) or oral cefuroxime fora minimum of 2 months.  CONCLUSIONSMelioidosis can manifest as an ocular infection in both the anterior andposterior segments of the eye. The diagnosis is clinical in nature and early empiricaltherapy should be commenced whilst awaiting confirmatory serology results. Keywords:Ocular; infection; Melioidosis; Burkholderia pseudomallei                         INTRODUCTION Melioidosis is an infectiousdisease caused by the aerobic bacteria Burkholderia pseudomallei.

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It is endemic in tropical regions like South EastAsia and Northern Australia and can result in multi-system infection. Themanifestations of the infection are extremely vast, ranging from ocularinfections to soft tissue infections, septicemia, pneumonia, osteomyelitis andcentral nervous system infection. Burkholderia pseudomalleiis the causative agent in a host of multi system infections.

 We report a case series of threepatients who were treated for ocular Melioidosis based on clinical features andpositive serology tests for Burkholderia pseudomallei. METHODSThis was a restrospective caseseries of 3 patients with ocular Melioidosis who presented to Hospital Selayangfrom 2013-2016.The demographic details (age andgender), case notes, anterior segment and fundus photographs, bloodinvestigations and ocular investigations were analyzed.

All patients hadserological testing for Burkholderia pseudomallei (IGM levels) which was sentto Institiute of Medical Research, Kuala Lumpur for analysis.     RESULTS CASE 1  A healthy33-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 Melioidosissuch as diabetes mellitus, open wounds and environmental or occupationalexposure 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 haddiffuse injection and superotemporal scleral tenderness. The anterior chamberwas deep, with plasmoid,fibrinous aqueous, cellular activity of 4+and a streakof hypopyon. (Figure 1). Fundus examination revealed a normal optic disc, butdetails of the fundus in the RE were obscured by the anterior media opacity. OnB scan ultrasonography, there were no vitreous opacities or loculations andT-sign was absent. The left eye findings were unremarkable. Diagnosis of righteye severe anterior sclerouveitis was made.She was commenced on Guttdexamethasone hourly, Gutt homatropine 8 hourly and T.

ibuprofen 400mg 12hourly. Blood investigations revealed mild leukocytosis. As the hypopyon levelappeared to be rising, she was commenced on intravenous ceftazidime 1gm 12hourly, hourly Gutt moxifloxacin 0.5% and given intracameral moxifloxacin.  Meanwhile the serology forBurkholderia pseudomallei returned positive. Blood and aqueous fluidcultures were negative. After 4 days of IV Ceftazidime, the VA OD improved to6/12. 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 ODimproved 6/9 unaided, with normal ocular findings.  CASE 2 A healthy 21-year-old lady with nopast medical history was referred for a 4-month history of redness and pain inthe left eye, which was initially treated as anterior uveitis. Her bloodinvestigations were positive for toxoplasma IgM, so she had been treated withoral 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, OSwas HM. The right eye was normal. Intraocular pressures were also normal.

Lefteye examination revealed keratic precipitates, cellular activity of 1+,posterior synechiae and posterior subcapsular cataract. Fundus examination OSrevealed a swollen optic disc, oedematous macula with a partial macular starand vitritis. (Figure 2) Optical coherencetopography demonstrated intraretinal and subretinal fluid OS. She was commenced on oral doxycycline100mg 12 hourly as well as Gutt dexamethasone 4hourly and G homatropine 8hourly. Initially there was improvement; however, a few weeks later her visiondeteriorated further and there was increase of cellular activity and vitritis.She was empirically started on IV ceftazidime 1gm 12 hourly which was given for6 days and Gutt moxifloxacin 4hourly.Systemic prednisolone was started tohasten the resolution of exudation.

Repeat investigations includinginfective screening, blood and urine cultures were negative. At this juncture,the serology for Burkholderia pseudomallei returned positive. As her condition improved, thesteroids were tapered off.

She then completed two months of Oral bactrim (trimethoprin+ sulfamethoxazole) 960mg 12 hourly. Repeated serology of Burkholderia pseudomallei was negative.She wasscheduled for LE synechiolysis with cataract extraction and IOL insertion. On her pre-operative assessment 2months later, both eyes had cells of 3+.VA was 6/12 OD and CF 1ft OS.The REfundus examination revealed a hyperemic optic disc and macula striation; however,there was no vitritis or retinitis.

The repeated Burkholderia pseudomalleiserology was positive with a titre of 1:160. IV ceftazidime 1gm 12 hourly was given for 14 days, followed by oral bactrimfor 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 wasanterior chamber reaction of 3+ bilaterally and a hyperemic disc OD.  Fundus fluorescein angiogram OD revealedleakage from the disc, perifoveal vasculitis and small vessel vasculitis in allquadrants, but no areas of capillary non-perfusion.  Repeated Burkholderia serology now wasnegative, however, she was noted to have positive Bartonella hensei serology.

She was started on Oral doxycycline 100mg 12 hourly. She subsequently defaultedfollow up.    CASE 3A healthy 10-year-old boy presentedwith a 2-week history of bilateral eye redness, tearing and generalizedblurring of vision, which was preceded by fever that resolved with oralantibiotics and anti-pyretics. He had history of camping 2 months ago. Onexamination, 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 andsheathing in all 4 quadrants with macula striation. (Figure 3).

There was noobvious retinitis or choroiditis. He was commenced on Gutt dexamethasone 2hourlyand Gutt homatropine 8hourly for BE whilst awaiting his blood investigationresults. On review 2 days later, his symptoms remained the same, as did theocular findings. Baseline blood investigations and work up for Tuberculosiswere normal. He was admitted for BE endogenous endophthalmitis and started onIV ceftazidime 25mg/kg 8hourly and Gutt moxifloxacin 2hourly BE.

Aftercompletion of one week of IV ceftazidime, his symptoms improved and VA BEimproved to 6/9, with cellular reaction of 1+, with resolving periphlebitis andoptic disc swelling. Burkholderia pseudomallei serology returned positive. Hewas discharged with oral cefuroxime 250mg 12 hourly after consulting with thepediatrician. 1 month later his VA had improved to 6/6 BE with no cellularactivity and resolution of vasculitis in both eyes. He completed 8 weeks oforal cefuroxime and repeat Burkholderia serology was negative. His final VA was6/6 BE with normal ocular findings.              Figure 1 (Case 1)Anteriorsegment photograph showing conjunctival hyperemia with hypopyon OD                 Figure 2 (Case 2)Fundus photo OS a showing swollenoptic disc, macular oedema, partial macular star and vitritis               Figure 3 (Case 3)Fundus photo OS showing periphlebitis andoptic disc swelling                DISCUSSION Burkholderia pseudomalleiis 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- sporeforming, aerobic gram  negative bacillus which is mostly found in soil and water.(1) Infections secondary to theorganism occur following exposure via inhalation, ingestion or skininoculation to contaminated soil or water.(2) Transmission may rarely occur via contact with infectedblood 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).Otherrisk 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, bacteremiaor 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 infectionoccurring in healthy  immunocompetent individuals without predisposing factors. (7)  The widespectrum of clinical symptoms, signs and infection sites has earned Melioidosisthe title of  the “great mimicker”.

(1, 3, 5) This description hasbeen used to describe the multi-system  involvementof Melioidosis, however the ocular manifestations of this infection have rarelybeen  reportedin the literature. Our case series demonstrates that just like otherMelioidosis infections with  multisystem involvement, isolated ocular Melioidosis can present with various manifestations.The  widespectrum of presentations and lack of clinical evidence of systemic infectionrenders it a complex clinicalproblem and poses a diagnostic challenge.  This case series involved 3 patientswith no systemic evidence of Melioidosis who presented with ocular symptomsattributed to Burkholderia pseudomallei, as evidenced by the positive serologyresults and good response to treatment with intravenous ceftazidime. All thepatients were young and healthy with no history of diabetes mellitus orimmunosuppression. Two out of the 3 patients had risk factors that may havecontributed to the ocular infection (exposure to blood and history of campingthus having environmental exposure to soil and water), athough there was nohistory of open wounds on the skin.

 In case 1, theocular findings were confined to the anterior segment, however in cases 2 &3, there was both anterior and posterior segment involvement, with intenseinflammation. Ocular fluid (aqueous) was sent for culture in case 1, but didnot yield any positive result. This could be due to the scarce volume of fluid availablefor sampling, resulting in a low yield.  The prevailinggold standard of confirming a clinical diagnosis of Melioidosis is by isolatingBurkholderia pseudomallei from clinical specimens.(8, 9)Serological testing is beneficial in endemic areas as it can be used as apreliminary test whilst awaiting positive culture reports which may be timeconsuming and cause a delay in treatment, however the sensitivity rates arelower than cultures. Examples of serological tests for Melioidosis include indirecthemagglutination 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 treatmentwas commenced whilst awaiting confirmatory serological tests for Burkholderiapseudomallei.

Cases 1 & 3 showed good response to treatment with goodvisual outcomes and no sequelae; Case 2 however defaulted treatment and followup. The patient in case 2 sought treatment late, hence further diagnosis andtreatment were also delayed. The recommended treatment for severesepticemic Melioidosis involves a combination of high dose intravenous ceftazidimeand trimethoprim-sulphamethoxazole for up to 2 to 4 weeks as the immediate formof therapy , followed by an eradication phase with trimethoprim-sulphamethoxazoleor 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 standardantimicrobial regimes used in combination with topical steroids, as there wasreduction of inflammation and clinical signs after a few days of intravenousceftazidime in all 3 cases.  The commonest form of presentationof ocular Melioidosis is severe uveitis (which was seen in all 3 cases) and thecases were isolated, without any obvious clues of risks or systemic findings.As ocular Melioidosis can occur in healthy individuals in endemic areas, it isimperative to include Melioidosis serology as a routine blood investigation, asa delay in diagnosis can result in poor visual outcomes, as seen in case 2. Melioidosis is known in Malaysiafor the wide range of systemic infections and it remains a difficult infectionto diagnose given its many presentations.

As with other forms of Melioidosis,the ocular variant which is localized to the eye may present with various formsof uveitis in a healthy individual. Early treatment can result in completeresolution of infection with no sequelae.  ConclusionOcular Melioidosis is commonlyunderdiagnosed in endemic areas and should be suspected in any severe form ofuveitis, especially those which do not respond to the initial treatment. Empircaltherapy can be initiated whilst awaiting confirmatory serological testing.                                  REFERENCES