NRU :: Browsing by Author "Leck, Astrid"

Browsing by Author "Leck, Astrid"

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Bilateral Candida keratitis in an HIV patient with asymptomatic genitourinary candidiasis in Uganda
(Medical mycology case reports, 2018) Arunga, Simon; Kwaga, Teddy; Leck, Astrid; Hub, Victor H.; Burton, Matthew J.
A 35-year-old male presented with Candida keratitis in the left eye. He was HIV positive with a CD4 of 352 cells/ μL. The eye quickly deteriorated, despite intensive antifungal treatment and was eviscerated. Five months later, he re-presented with Candida keratitis in his right eye. A focal source of Candida infection was suspected and a urine culture identified Candida spp, despite being asymptomatic for genitourinary candidiasis. He was subsequently treated with good outcome (max. 75 words)
Chlorhexidine gluconate 0.2% as a treatment for recalcitrant fungal keratitis in Uganda: a pilot study
(BMJ open ophthalmology, 2021) Arunga, Simon; Mbarak, Tumu; Ebong, Abel; Mwesigye, James; Kuguminkiriza, Dan; Mohamed-Ahmed, Abeer H. A.; John Hoffman, Jeremy; Leck, Astrid; Hu, Victor; Burton, Matthew
Fungal keratitis is a major ophthalmic public health problem, particularly in low-income and middle-income countries. The options for treating fungal keratitis are limited. Our study aimed to describe the outcomes of using chlorhexidine 0.2% eye-drops as additional treatment in the management of patients with recalcitrant fungal keratitis. Methods This study was nested within a large cohort study of people presenting with microbial keratitis in Uganda. We enrolled patients with recalcitrant fungal keratitis not improving with topical natamycin 5% and commenced chlorhexidine 0.2%. Follow-up was scheduled for 3 months and 1 year. The main outcome measures were healing, visual acuity and scar size at final follow-up. Results Thirteen patients were followed in this substudy. The patients were aged 27–73 years (median 43 years). Filamentous fungi were identified by microscopy of corneal scrape samples in all cases. Isolated organisms included Aspergillus spp, Fusarium spp, Candida spp, Bipolaris spp and Acremoninum spp. At the final follow-up, nine patients (75%) had healed; three had vision of better than 6/18. Three patients lost their eyes due to infection. In the remaining nine cases, corneal scarring was variable ranging from 4.6 to 9.4 mm (median 6.6 mm, IQR 5.9–8.0 mm); of these five had dense scars, three had moderate scars and one had a mild scar. None of the patients demonstrated signs of chlorhexidine toxicity during the follow-up. Conclusion Chlorhexidine 0.2% was found to be a useful sequential adjunctive topical antifungal in cases of fungal keratitis not responding to natamycin 5%, which warrants further evaluation.
Delay in accessing definitive care for patients with microbial keratitis in Nepal
(Frontiers in Medicine, 2022) Hoffman, Jeremy J.; Yadav, Reena; Das Sanyam, Sandip; Chaudhary, Pankaj; Roshan, Abhishek; Singh, Sanjay K.; Mishra, Sailesh K.; Arunga, Simon; Hu, Victor H.; Macleod, David; Leck, Astrid; Burton, Matthew J.
The aim of this study was to describe the health-seeking journey for patients withmicrobial keratitis (MK) in Nepal and identify factors associated with delay. Methods: Prospective cohort study where MK patients attending a large, tertiary-referral eye hospital in south-eastern Nepal between June 2019 and November 2020 were recruited. We collected demographic details, clinical history, and examination findings. Care-seeking journey details were captured including places attended, number of journeys, time fromsymptomonset, and costs.We compared “direct” with “indirect” presenters, analyzing for predictors of delay. Results: We enrolled 643 patients with MK. The majority (96%) self-referred. “Direct” attenders accounted for only 23.6% (152/643) of patients, the majority of “indirect” patients initially presented to a pharmacy (255/491). Over half (328/643) of all cases presented after at least 7 days. The total cost of care increased with increasing numbers of facilities visited (p < 0.001). Those living furthest away were least likely to present directly (p < 0.001). Factors independently associated with delayed presentation included distance >50 km from the eye hospital [aOR 5.760 (95% CI 1.829–18.14, p = 0.003)], previous antifungal use [aOR 4.706 (95% CI 3.139–5.360)], and two or more previous journeys [aOR 1.442 (95% CI 1.111–3.255)]. Conclusions: Most patients visited at least one facility prior to our institution, with time to presentation and costs increasing with the number of prior journeys. Distance to the eye hospital is a significant barrier to prompt, direct presentation. Based on these findings, improving access to eye care services, strengthening referral networks and encouraging early appropriate treatment are recommended to reduce delay, ultimately improving clinical outcomes.
Diagnosis of Fungal Keratitis in Low-Income Countries: Evaluation of Smear Microscopy, Culture, and In Vivo Confocal Microscopy in Nepal
(Journal of Fungi, 2022) Hoffman, Jeremy J.; Yadav, Reena; Das Sanyam, Sandip; Chaudhary, Pankaj; Roshan, Abhishek; Kumar Singh, Sanjay; Arunga, Simon; Hu, Victor H.; Macleod, David; Leck, Astrid; Burton, Matthew J.
Clinically diagnosing fungal keratitis (FK) is challenging; diagnosis can be assisted by investigations including in vivo confocal microscopy (IVCM), smear microscopy, and culture. The aim of this study was to estimate the sensitivity in detecting fungal keratitis (FK) using IVCM, smear microscopy, and culture in a setting with a high prevalence of FK. In this cross-sectional study nested within a prospective cohort study, consecutive microbial keratitis (MK) patients attending a tertiary-referral eye hospital in south-eastern Nepal between June 2019 and November 2020 were recruited. IVCM and corneal scrapes for smear microscopy and culture were performed using a standardised protocol. Smear microscopy was performed using potassium hydroxide (KOH), Gram stain, and calcofluor white. The primary outcomes were sensitivities with 95% confidence intervals [95% CI] for IVCM, smear microscopy and culture, and for each different microscopy stain independently, to detect FK compared to a composite referent. We enrolled 642 patients with MK; 468/642 (72.9%) were filamentous FK, 32/642 (5.0%) were bacterial keratitis and 64/642 (10.0%) were mixed bacterial-filamentous FK, with one yeast infection (0.16%). No organism was identified in 77/642 (12.0%). Smear microscopy had the highest sensitivity (90.7% [87.9–93.1%]), followed by IVCM (89.8% [86.9–92.3%]) and culture (75.7% [71.8–79.3%]). Of the three smear microscopy stains, KOH had the highest sensitivity (85.3% [81.9–88.4%]), followed by Gram stain (83.2% [79.7–86.4%]) and calcofluor white (79.1% [75.4–82.5%]). Smear microscopy and IVCM were the most sensitive tools for identifying FK in our cohort. In low-resource settings we recommend clinicians perform corneal scrapes for microscopy using KOH and Gram staining. Culture remains an important tool to diagnose bacterial infection, identify causative fungi and enable antimicrobial susceptibility testing.
Epidemiology of Microbial Keratitis in Uganda: A Cohort Study
(Ophthalmic Epidemiology, 2020) Arunga, Simon; Kintoki, Guyguy M.; Mwesigye, James; Ayebazibwe, Bosco; Onyango, John; Bazira, Joel; Newton, Rob; Gichuhi, Stephen; Leck, Astrid; Macleod, David; Hu, Victor H.; Burton, Matthew J.
To describe the epidemiology of Microbial Keratitis (MK) in Uganda. Methods: We prospectively recruited patients presenting with MK at two main eye units in Southern Uganda between December 2016 and March 2018. We collected information on clinical history and presentation, microbiology and 3-month outcomes. Poor vision was defined as vision < 6/60). Results: 313 individuals were enrolled. Median age was 47 years (range 18–96) and 174 (56%) were male. Median presentation time was 17 days from onset (IQR 8–32). Trauma was reported by 29% and use of Traditional Eye Medicine by 60%. Majority presented with severe infections (median infiltrate size 5.2 mm); 47% were blind in the affected eye (vision < 3/60). Microbiology was available from 270 cases: 62% were fungal, 7% mixed (bacterial and fungal), 7% bacterial and 24% no organism detected. At 3 months, 30% of the participants were blind in the affected eye, while 9% had lost their eye from the infection. Delayed presentation (overall p = .007) and prior use of Traditional Eye Medicine (aOR 1.58 [95% CI 1.04–2.42], p = .033) were responsible for poor presentation. Predictors of poor vision at 3 months were: baseline vision (aOR 2.98 [95%CI 2.12–4.19], p < .0001), infiltrate size (aOR 1.19 [95%CI 1.03–1.36], p < .020) and perforation at presentation (aOR 9.93 [95% CI 3.70–26.6], p < .0001). Conclusion: The most important outcome predictor was the state of the eye at presentation, facilitated by prior use of Traditional Eye Medicine and delayed presentation. In order to improve outcomes, we need effective early interventions.
The impact of microbial keratitis on quality of life in Uganda
(BMJ Open Ophthalmology, 2019) Arunga, Simon; Wiafe, Geoffrey; Habtamu, Esmael; Onyango, John; Gichuhi, Stephen; Leck, Astrid; Macleod, David; Hu, Victor; Burton, Matthew
Microbial keratitis (MK) is a frequent cause of sight loss in sub-Saharan Africa. However, no studies have formally measured its impact on quality of life (QoL) in this context. Methods As part of a nested case–control design for risk factors of MK, we recruited patients presenting with MK at two eye units in Southern Uganda between December 2016 and March 2018 and unaffected individuals, individually matched for sex, age and location. QoL was measured using WHO Health-Related and Vision-Related QoL tools (at presentation and 3 months after start of treatment in cases). Mean QoL scores for both groups were compared. Factors associated with QoL among the cases were analysed in a linear regression model. Results 215 case-controls pairs were enrolled. The presentation QoL scores for the cases ranged from 20 to 65 points. The lowest QoL was visual symptom domain; mean 20.7 (95% CI 18.8 to 22.7) and the highest was psychosocial domain; mean 65.6 (95% CI 62.5 to 68.8). At 3 months, QoL scores for the patients ranged from 80 to 90 points while scores for the controls ranged from 90 to 100. The mean QoL scores of the cases were lower than controls across all domains. Determinants of QoL among the cases at 3 months included visual acuity at 3 months and history of eye loss. Conclusion MK severely reduces QoL in the acute phase. With treatment and healing, QoL subsequently improves. Despite this improvement, QoL of someone affected by MK (even with normal vision) remains lower than unaffected controls.
The management of microbial keratitis within Uganda’s primary health system: a situational analysis [version 1; peer review: 3 approved]
(Wellcome Open Research, 2019) Arunga, Simon; Kyomugasho, Naome; Kwaga, Teddy; Onyango, John; Leck, Astrid; Macleod, David; Hu, Victor; Burton, Matthew
Microbial keratitis (MK) frequently leads to sight-loss, especially when the infection is severe and/or appropriate treatment is delayed. The primary health system as an entry point plays a central role in facilitating and directing patient access to appropriate care. The purpose of this study was to describe the capacity of primary health centres in Uganda in managing MK. Methods: We carried out a rigorous assessment of primary health centres and mid-cadre training schools in South Western Uganda. Through interviews, checklists and a picture quiz, we assessed capacity and knowledge of MK management. In addition, we interviewed the heads of all the mid-cadre training schools to determine the level of eye health training provided in their curricula. Results: In total, 163 health facilities and 16 training schools were enrolled. Of the health facilities, only 6% had an Ophthalmic Clinical Officer. Only 12% of the health workers could make a diagnosis of MK based on the clinical signs in the picture quiz. Although 35% of the facilities had a microscope, none reported doing corneal scraping. None of the facilities had a stock of the recommended first line treatment options for MK (ciprofloxacin and natamycin eye drops). Among the training schools, 15/16 had an eye health component in the curriculum. However, the majority (56%) of tutors had no formal expertise in eye health. In 14/16 schools, students spent an average of two weeks in an eye unit. Conclusions: Knowledge among health workers and capacity of health facilities in diagnosis and management of MK was low. Training for eye health within mid-cadre training schools was inadequate. More is needed to close these gaps in training and capacity.
The management of microbial keratitis within Uganda’s primary health system: a situational analysis [version 1; peer review: 3 approved]
(Wellcome Open Research, 2019) Arunga, Simon; Kyomugasho, Naome; Kwaga, Teddy; Onyango, John; Leck, Astrid; Macleod, David; Hu, Victor; Burton, Matthew
Microbial keratitis (MK) frequently leads to sight-loss, especially when the infection is severe and/or appropriate treatment is delayed. The primary health system as an entry point plays a central role in facilitating and directing patient access to appropriate care. The purpose of this study was to describe the capacity of primary health centres in Uganda in managing MK. Methods: We carried out a rigorous assessment of primary health centres and mid-cadre training schools in South Western Uganda. Through interviews, checklists and a picture quiz, we assessed capacity and knowledge of MK management. In addition, we interviewed the heads of all the mid-cadre training schools to determine the level of eye health training provided in their curricula. Results: In total, 163 health facilities and 16 training schools were enrolled. Of the health facilities, only 6% had an Ophthalmic Clinical Officer. Only 12% of the health workers could make a diagnosis of MK based on the clinical signs in the picture quiz. Although 35% of the facilities had a microscope, none reported doing corneal scraping. None of the facilities had a stock of the recommended first line treatment options for MK (ciprofloxacin and natamycin eye drops). Among the training schools, 15/16 had an eye health component in the curriculum. However, the majority (56%) of tutors had no formal expertise in eye health. In 14/16 schools, students spent an average of two weeks in an eye unit. Conclusions: Knowledge among health workers and capacity of health facilities in diagnosis and management of MK was low. Training for eye health within mid-cadre training schools was inadequate. More is needed to close these gaps in training and capacity.
Microbial Keratitis in Nepal: Predicting the Microbial Aetiology from Clinical Features
(Journal of Fungi, 2022) Hoffman, Jeremy J.; Yadav, Reena; Sanyam, Sandip Das; Chaudhary, Pankaj; Roshan, Abhishek; Kumar Singh, Sanjay; Arunga, Simon; Hu, Victor H.; Macleod, David; Leck, Astrid; Burton, Matthew J.
Fungal corneal infection (keratitis) is a common clinical problem in South Asia. However, it is often challenging to distinguish this from other aetiologies, such as bacteria or acanthamoeba. In this prospective study, we investigated clinical and epidemiological features that can predict the microbial aetiology of microbial keratitis in Nepal. We recruited patients presenting with keratitis to a tertiary eye hospital in lowland eastern Nepal between June 2019 and November 2020. A structured assessment, including demographics, history, and clinical signs, was carried out. The aetiology was investigated with in vivo confocal microscopy and corneal scrape for microscopy and culture. A predictor score was developed using odds ratios calculated to predict aetiology from features. A fungal cause was identified in 482/642 (75.1%) of cases, which increased to 532/642 (82.9%) when including mixed infections. Unusually, dematiaceous fungi accounted for half of the culture-positive cases (50.6%). Serrated infiltrate margins, patent nasolacrimal duct, raised corneal slough, and organic trauma were independently associated with fungal keratitis (p < 0.01). These four features were combined in a predictor score. The probability of fungal keratitis was 30.1% if one feature was present, increasing to 96.3% if all four were present. Whilst microbiological diagnosis is the “gold standard” to determine the aetiology of an infection, certain clinical signs can help direct the clinician to find a presumptive infectious cause, allowing appropriate treatment to be started without delay. Additionally, this study identified dematiaceous fungi, specifically Curvularia spp., as the main causative agent for fungal keratitis in this region. This novel finding warrants further research to understand potential implications and any trends over time.
Responding to COVID-19 in eye health
(Community Eye Health Journal, 2020) Hu, Victor; Kyari, Fatima; Prajna, N. Venkatesh; Leck, Astrid; Arunga, Simon; Habtamu, Esmael; Wolvaardt, Elmien; Philippin, Heiko
Millions of people have been infected with the SARS-CoV-2 virus and many have become seriously ill, threatening to overwhelm the ability of health systems to cope. Many lives have been lost – including those of health care workers.
Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial
(BMJ open, 2020) Hoffman, Jeremy John; Yadav, Reena; Das Sanyam, Sandip; Chaudhary, Pankaj; Roshan, Abhishek; Kumar Singh, Sanjay; Arunga, Simon; Matayan, Einoti; Macleod, David; Anne Weiss, Helen; Leck, Astrid; Hu, Victor; Burton, Matthew J.
Fungal infections of the cornea, fungal keratitis (FK), are challenging to treat. Current topical antifungals are not always effective and are often unavailable, particularly in low-income and middle-income countries where most cases occur. Topical natamycin 5% is usually first-line treatment, however, even when treated intensively, infections may progress to perforation of the eye in around a quarter of cases. Alternative antifungal medications are needed to treat this blinding disease. Chlorhexidine is an antiseptic agent with antibacterial and antifungal properties. Previous pilot studies suggest that topical chlorhexidine 0.2% compares favourably with topical natamycin. Full-scale randomised controlled trials (RCTs) of topical chlorhexidine 0.2% are warranted to answer this question definitively. Methods and analysis We will test the hypothesis that topical chlorhexidine 0.2% is non-inferior to topical natamycin 5% in a two-arm, single-masked RCT. Participants are adults with FK presenting to a tertiary ophthalmic hospital in Nepal. Baseline assessment includes history, examination, photography, in vivo confocal microscopy and cornea scrapes for microbiology. Participants will be randomised to alternative topical antifungal treatments (topical chlorhexidine 0.2% and topical natamycin 5%; 1:1 ratio, 2–6 random block size). Patients are reviewed at day 2, day 7 (with reculture), day 14, day 21, month 2 and month 3. The primary outcome is the best spectacle corrected visual acuity (BSCVA) at 3 months. Primary analysis (intention to treat) will be by linear regression, with treatment arm and baseline BSCVA prespecified covariates. Secondary outcomes include epithelial healing time, scar/infiltrate size, ulcer depth, hypopyon size, perforation and/or therapeutic penetrating keratoplasty (corneal transplant), positive reculture rate (day 7) and quality of life (EuroQol-5 dimensions, WHO/ PBD-VF20, WHOQOL-BREF). Ethics and dissemination The Nepal Health Research Council, the Nepal Department of Drug Administration and the London School of Hygiene and Tropical Medicine ethics committee have approved the trial. The results
Topical Chlorhexidine 0.2% versus Topical Natamycin 5% for the Treatment of Fungal Keratitis in Nepal: A Randomized Controlled Noninferiority Trial
(Ophthalmology, 2022) Hoffman, Jeremy J.; Yadav, Reena; Sanyam, Sandip D.; Chaudhary, Pankaj; Roshan, Abhishek; Singh, Sanjay K.; Singh, Sanjay K.; Mishra, Sailesh K.; Arunga, Simon; Hu, Victor H.; Macleod, David; Leck, Astrid; Burton, Matthew J.
To investigate if topical chlorhexidine 0.2%, which is low cost and easy to formulate, is noninferior to topical natamycin 5% for the treatment of filamentous fungal keratitis. Design: Randomized controlled, single-masked, noninferiority clinical trial. Participants: Adults attending a tertiary-level ophthalmic hospital in Nepal with filamentous fungal infection confirmed on smear or confocal microscopy. Methods: Participants were randomly allocated to receive topical chlorhexidine 0.2% or topical natamycin 5%. Primary analysis (intention-to-treat) was by linear regression, using baseline logarithm of the minimum angle of resolution (logMAR) best spectacle-corrected visual acuity (BSCVA) and treatment arm as prespecified covariates. Mixed fungal-bacterial infections were excluded from the primary analysis but included in secondary analyses and secondary safety-related outcomes. The noninferiority margin was 0.15 logMAR. This trial was registered with ISRCTN, number ISRCTN14332621. Main Outcome Measures: The primary outcome measure was BSCVA at 3 months. Secondary outcome measures included perforation or therapeutic penetrating keratoplasty by 90 days. Results: Between June 3, 2019, and November 9, 2020, 354 eligible participants were enrolled and randomly assigned: 178 to chlorhexidine and 176 to natamycin. Primary outcome data were available for 153 and 151 of the chlorhexidine and natamycin groups, respectively. Of these, mixed bacterial-fungal infections were found in 20 cases (12/153 chlorhexidine, 8/151 natamycin) and excluded from the primary analysis. Therefore, 284 patients were assessed for the primary outcome (141 chlorhexidine, 143 natamycin). We did not find evidence to suggest chlorhexidine was noninferior to natamycin and in fact found strong evidence to suggest that natamycin-treated participants had significantly better 3-month BSCVA than chlorhexidine-treated participants, after adjusting for baseline BSCVA (regression coefficient, 0.30; 95% confidence interval [CI], 0.42 to 0.18; P < 0.001). There were more perforations and emergency corneal grafts in the chlorhexidine arm (24/175, 13.7%) than in the natamycin arm (10/173, 5.8%; P ¼ 0.018, mixed infections included), whereas natamycin-treated cases were less likely to perforate or require an emergency corneal graft, after adjusting for baseline ulcer depth (odds ratio, 0.34; 95% CI, 0.15e0.79; P ¼ 0.013). Conclusions: Treatment with natamycin is associated with significantly better visual acuity, with fewer adverse events, compared with treatment with chlorhexidine. Natamycin remains the preferred first-line monotherapy treatment for filamentous fungal keratitis. Ophthalmology 2022;129:530-541 ª 2021 by the American Academy of Ophthalmology.
Traditional eye medicine use in microbial keratitis in Uganda: a mixed methods study [version 1; peer review: awaiting peer review]
(Wellcome open research, 2019) Arunga, Simon; Asiimwe, Allen; Apio Olet, Eunice; Kagoro-Rugunda, Grace; Ayebazibwe, Bosco; Onyango, John; Newton, Robert; Leck, Astrid; Macleod, David; Hu, Victor H.; Seeley, Janet; Burton, Matthew J.
Traditional eye medicine (TEM) is frequently used to treat microbial keratitis (MK) in many parts of Africa. Few reports have suggested that this is associated with a worse outcome. We undertook this large prospective study to determine how TEM use impacts presentation and outcome of MK and to explore reasons why people use TEM for treatment in Uganda. Methods: In a mixed method prospective cohort study, we enrolled patients presenting with MK at the two main eye units in Southern Uganda between December 2016 and March 2018 and collected information on history, TEM use, microbiology and 3-month outcomes. We conducted qualitative interviews with patients, carers traditional healers on reasons why people use TEM. Outcome measures included presenting vision and at 3-months, comparing TEM Users versus Non-Users. A thematic coding framework was deployed to explore reasons for use of TEM. Results: 188 out of 313 participants reported TEM use. TEM Users had a delayed presentation; median presenting time 18 days versus 14 days, p= 0.005; had larger ulcers 5.6 mm versus 4.3 mm p=0.0005; a worse presenting visual acuity median logarithm of the minimum angle of resolution (Log MAR) 1.5 versus 0.6, p=0.005; and, a worse visual acuity at 3 months median Log MAR 0.6 versus 0.2, p=0.010. In a multivariable logistic regression model, distance from the eye hospital and delayed presentation were associated with TEM use. Reasons for TEM use included lack of confidence in conventional medicine, health system breakdown, poverty, fear of the eye hospital, cultural belief in TEM, influence from traditional healers, personal circumstances and ignorance. : TEM users h Conclusion ad poorer clinical presentation and outcomes. Capacity building of the primary health centres to improve access to eye care and community behavioural change initiatives against TEM use should be encouraged.

Browsing by Author "Leck, Astrid"

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