Background: A multicentre study was carried out in Ghana and southern India to determine the aetiology of suppurative keratitis in two regions located at similar tropical latitudes. Studies of fungal keratitis from the literature were reviewed. Methods: Patients presenting at rural and urban eye units with suspected microbial keratitis were recruited to the study. Corneal ulceration was defined as loss of corneal epithelium with clinical evidence of infection with or without hypopyon. Microscopy and culture were performed on all corneal specimens obtained. Results: 1090 patients were recruited with suspected microbial keratitis between June 1999 and May 2001. Overall the principal causative micro-organisms in both regions were filamentous fungi (42%): Fusarium species and Aspergillus species were the commonest fungal isolates. Pseudomonas species were most frequently isolated from cases of bacterial keratitis in Ghana but in India the commonest bacterial isolates were streptococci. Conclusion: Infections of the cornea due to filamentous fungi are a frequent cause of corneal damage in developing countries in the tropics and are difficult to treat. Microscopy is an essential tool in the diagnosis of these infections. A knowledge of the “local” aetiology within a region is of value in the management of suppurative keratitis in the event that microscopy cannot be performed.

Aim: To assess whether the presence of characteristic clinical features can be used as a diagnostic aid for suppurative keratitis caused by filamentous fungi. Methods: Patients presenting with suppurative keratitis in India underwent detailed clinical examination followed by microbiological investigation of corneal scrapes. A partial diagnostic score based upon the strength of the association, as estimated by the odds ratio, between reported clinical features and laboratory confirmed diagnoses was devised and subsequently tested using a case series from Ghana. Results: Serrated margins, raised slough, dry texture, satellite lesions and coloration other than yellow occurred more frequently in cases of filamentous fungal keratitis than bacterial keratitis (p<0.05). Hypopyon and fibrinous exudate were observed more frequently in bacterial keratitis (p<0.05). When incorporated into a backwards stepwise logisitic regression model only serrated margins, raised slough, and colour were independently associated with fungal keratitis; these features were used in the scoring system. The probability of fungal infection if one clinical feature was present was 63%, increasing to 83% if all three features were present. Conclusions: Microbiological investigations should be performed whenever possible; however, where facilities are not available, a rapid presumptive diagnosis of suppurative keratitis may be possible by scoring clinical features.

Mycotic or fungal keratitis (FK) is a sight-threatening disease, caused by infection of the cornea by filamentous fungi or yeasts. In tropical, low and middle-income countries, it accounts for the majority of cases of microbial keratitis (MK). Filamentous fungi, in particular Fusarium spp., the aspergilli and dematiaceous fungi, are responsible for the greatest burden of disease. The predominant risk factor for filamentous fungal keratitis is trauma, typically with organic, plant-based material. In developed countries, contact lens wear and related products are frequently implicated as risk factors, and have been linked to global outbreaks of Fusarium keratitis in the recent past. In 2020, the incidence of FK was estimated to be over 1 million cases per year, and there is significant geographical variation; accounting for less than 1% of cases of MK in some European countries to over 80% in parts of south and south-east Asia. The proportion of MK cases is inversely correlated to distance from the equator and there is emerging evidence that the incidence of FK may be increasing. Diagnosing FK is challenging; accurate diagnosis relies on reliable microscopy and culture, aided by adjunctive tools such as in vivo confocal microscopy or PCR. Unfortunately, these facilities are infrequently available in areas most in need. Current topical antifungals are not very effective; infections can progress despite prompt treatment. Antifungal drops are often unavailable. When available, natamycin is usually first-line treatment. However, infections may progress to perforation in ~25% of cases. Future work needs to be directed at addressing these challenges and unmet needs. This review discusses the epidemiology, clinical features, diagnosis, management and aetiology of FK.

Objective: To identify the timing, pattern, and determinants of colonization of neonates byMalassezia.Design: Prospective observational study.Setting: A neonatal medical and surgical unit consisting of 10 special care, 10 high-dependency, 10 intensive care, and 10 surgical cots.Participants: All neonates (≤ 28 days of age) or infants (> 28 days of age) admitted to the unit during the 20-week period from October 1995 to March 1996.Methods: All infants or neonates were swabbed on the day of admission and every third day thereafter and risk factors were collected for every day on the unit.Results: During the study period, 245 neonates and 42 infants were sampled for their entire duration of stay on the unit. Of these, 41 infants (97.6%) were colonized withMalasseziaon admission to the unit and thereafter, as assessed by subsequent samples. Within the neonate population, 78 (31.8%) became colonized, but none were colonized immediately after birth. Univariate analysis showed that many factors appeared to be significantly associated with colonization in the neonates, including use of ventilation, presence of central venous catheters, use of parenteral nutrition, and use of antibacterial or antifungal drugs. However, when the data were analyzed by multivariate logistic regression to control for confounding variables, only gestational age and length of stay on the unit were found to be significantly associated with colonization.Conclusion: Colonization of infants is not as unusual as previously thought and many infants have established a cutaneousMalasseziacommensal flora by the age of 3 to 6 months. Factors that predispose to colonization in neonates may not be the same as those that predispose to infection.

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. Randomized controlled, single-masked, noninferiority clinical trial. Adults attending a tertiary-level ophthalmic hospital in Nepal with filamentous fungal infection confirmed on smear or confocal microscopy. 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. The primary outcome measure was BSCVA at 3 months. Secondary outcome measures included perforation or therapeutic penetrating keratoplasty by 90 days. 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 = 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, 0.15–0.79; P = 0.013). 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.

Purpose: To describe the care seeking journey and causes of delay among patients with Microbial Keratitis in Uganda. Methods: A prospective cohort of patients presenting with microbial keratitis at the two main eye units in Southern Uganda (2016–2018). We collected information on demographics, home address, clinical history, and presentation pathway including, order of facilities where patients went to seek care, treatment advice, cost of care, and use of Traditional Eye Medicine. Presentation time was noted. We compared “direct” presenters versus “indirect” presenters and analysed predictors of delay. Results: About 313 patients were enrolled. All were self-referred. Only 19% of the patients presented directly to the eye hospital. Majority (52%) visited one facility before presenting, 19% visited two facilities, 9% visited three facilities, and 2% visited four facilities. The cost of care increased with increase in the number of facilities visited. People in a large household, further distance from the eye hospital and those who used Traditional Eye Medicine were less likely to come directly to the eye hospital. Visiting another facility prior to the eye hospital and use of Traditional Eye Medicine aOR 1.58 (95%CI 1.03–2.43), p = .038 were associated with delayed presentation to the eye hospital. Conclusion: This study provided information on patient journeys to seek care. Delay was largely attributable to having visited another health facility: a referral mechanism for microbial keratitis was non-existent. There is need to explore how these health system gaps can be strengthened.