Epidemiology of Microbial Keratitis in Uganda: A Cohort Study

Figures & data

Table 1. Demographic characteristics of the study participants.

Variable	n/313	(%)
Age (median = 47, IQR 35–60) in years
< 30 years	54	(17%)
30–40 years	63	(20%)
40–50 years	59	(19%)
50–60 years	66	(21%)
> 60 years	71	(23%)
Gender
Female	139	(44%)
Male	174	(56%)
Occupation
Farmer	220	(70%)
Non-farmer	93	(30%)
Education
None	84	(27%)
Primary level	162	(52%)
Secondary level	45	(14%)
Tertiary level	22	(7%)
Marital status
Unmarried^a	95	(30%)
Married	218	(70%)
Economic status^b
Lower	85	(28%)
Middle	189	(63%)
Upper	26	(9%)
Being head of household
Yes	212	(68%)
No	101	(32%)
Distance from the eye hospital (median = 79 km IQR 52–128)
0–50 km	77	(25%)
50–100 km	111	(35%)
100–150 km	75	(24%)
>150 km	50	(16%)
Nearest health center (Median 3 km, IQR 1–4 km)^c
Clinic	10	(3%)
HC II	103	(33%)
HC III	96	(31%)
HC IV	43	(14%)
Hospital	32	(10%)
Don’t know	29	(9%)

^aUnmarried included single divorced and widowed.

^bEconomic status was self-reported where participants compared themselves with their neighborhood as “poor”, “neither poor nor rich” or “rich”, n was 300 with 13 non-reported values.

^cThe nearest health center was the health center that the patients considered nearest to them regardless of the level of that health center

Figure 1. Flow diagram of participants who were enrolled in the cohort study.

Figure 2. Presentation of patients with MK, by month in 2017 (n = 261). Monthly average minimum and maximum temperatures, average humidity and the number of days with rain are overlaid. Humidity was in percentage but was scaled to tens (divided by 10) to fit on the plot scale.

Table 2. Clinical history.

Variable	n/313	(%)
Presenting time (median = 17 days, IQR 8–32)^a
Prompt 0–3 days	23	(7%)
Early 4–7 days	46	(15%)
Intermediate 8–14 days	72	(23%)
Late 15–30 days	79	(26%)
Very late >30 days	90	(29%)
Most important symptom (self-reported)
Pain	144	(46%)
Reduced vision	137	(44%)
Other	32	(10%)
History of trauma
Yes	91	(29%)
No	220	(71%)
Used traditional eye medicine
Yes	188	(60%)
No	125	(40%)
Used other treatment^b
Yes	275	(88%)
No	38	(12%)
Diabetic (n = 280)^c	22	(8%)
HIV positive (n = 284)^c	37	(13%)

^an was 310. For 3 patients the date of onset could not be well ascertained.

Some patients had used other forms of eye drops prior to presentation and there was some overlap among those who used TEM and other eye drops.

^bIt was not possible to ascertain the forms of other treatment used.

^cSome patients declined to be tested for HIV and diabetes

Table 3. Clinical features and diagnosis at presentation (n = 313).

Variable	Median	(IQR [Total Range])
Infiltrate size (mm)^a	5.2	(3.3–7.7 [0.5–13])
Epithelial defect size (mm)^a	3.9	(2.4–6.5 [0–14])
Variable	n/313	(%)
Snellen Visual Acuity in affected eye(n = 312)
6/5–6/18	102	(33%)
6/24–6/60	42	(12%)
5/60–3/60	24	(8%)
2/60–1/60	33	(11%)
Counting fingers-light perception	103	(33%)
No light perception	9	(3%)
Snellen visual acuity in non-affected eye (n = 312)
6/5–6/18	278	(89%)
6/24–6/60	16	(5%)
5/60–3/60	2	(1%)
2/60–1/60	4	(1.2%)
Counting fingers-light perception	6	(2%)
No light perception	6	(1.8%)
Slough (n = 312)^b
No slough	62	(20%)
Flat	124	(40%)
Raised	126	(40%)
Infiltrate edge (n = 293)
Defined	35	(12%)
Serrated	258	(82%)
Not visible	20	(6%)
Satellite lesions present (n = 304)
Yes	178	(57%)
No	126	(40%)
Infiltrate colour (n = 288)
White	148	(47%)
Cream	106	(34%)
Other colour	34	(11%)
Hypopyon (median height 1.3mm IQR 0.9–2.9, n = 301)
Yes	94	(30%)
No	217	(69%)
Site of ulcer (n = 310)^c
Peripheral	27	(9%)
Paracentral	64	(21%)
Central	219	(70%)
Perforation status
Not perforated	237	(76%)
Impending	31	(10%)
Perforated	48	(12%)
Perforated & sealed	7	(2%)
Overall Laboratory diagnosis (n = 270)^d
Unknown	65	(21%)
Bacterial	20	(6%)
Fungal	168	(54%)
Mixed (bacteria/fungal)	17	(5%)

Where n < 313 was due to some missing data: percentages calculated for 313 and rounded off to the nearest whole number.

^aThese were calculated as the geometrical means using the MUTT protocol. The upper limits exceeded normal corneal diameter for some lesions, which extended up to the sclera.

^bRaised slough was when the corneal infiltrate profile was raised, flat slough was when the profile was flat while no slough is when there was no debris noted.

^cSite of ulcer was peripheral when the ulcer was marginal, paracentral was when the ulcer was not marginal but not within 4 mm of the center of the cornea, central was when the ulcer was within the central 4 mm of the cornea.

Impending perforation is when the clinicians felt the ulcer would perforate in the next 48 h.

^dSpecimen for microbiology was collected in 270 patients. Due to limited amounts of sample material, it was not possible to perform all tests on all those sampled. The order of material collection was 3 slide smears (gram, KOH, CFW), 3 agar inoculations (blood, chocolate, PDA) and 1 broth (BHI) depending on available material.

Table 4. Outcomes at 3 months.

Variable	n/260	(%)
Visual acuity in the affected eye (Snellen)
6/5–6/18	138	(53%)
6/24–6/60	37	(14%)
5/60–3/60	7	(3%)
2/60–1/60	14	(5%)
Counting fingers-light perception	31	(12%)
No light perception	33	(13%)
Visual acuity in the non-affected eye
6/5–6/18	229	(90%)
6/24–6/60	11	(4%)
5/60–3/60	2	(1%)
2/60–1/60	0	(0%)
Counting fingers-light perception	6	(2%)
No light perception	7	(3%)
Outcome
Healed no scar	34	(12%)
Healed mild scar	83	(30%)
Healed moderate scar	65	(24%)
Healed dense scar	46	(17%)
Eviscerated	24	(9%)
Not healed	20	(7%)
Staphyloma	4	(1%)

Table 5. Causal modeling for poor presenting vision (n = 313).

Variable	Univariable Analysis			Multivariable Analysis			Multivariable analysis for direct effect
	Crude OR^a	(95% CI)	p-value	Adj. OR	(95% CI)	p-value	OR	(95% CI)	p-value
Model 1: Used Traditional Eye Medicine (TEM) as the main exposure of interest^b
Used traditional eye medicine (TEM)	1.78	(1.17–2.70)	0.007	1.62	(1.04–2.54)	0.033	1.47	0.91–2.38	0.11
Model 2: Delayed presentation as the main exposure of interest^c
Prompt 0–3 days	1		0.0004	1		0.033
Early 4–7 days	2.78	(1.07–7.20)		1.94	(0.70–5.39)
Intermediate 8–14 days	4.45	(1.84–10.7)		3.02	(1.17–7.79)
Late 15–30 days	5.58	(2.33–13.3)		3.57	(1.40–9.07)
Very late > 30 days	2.63	(1.11–6.25)		1.87	(0.74–4.72)
Model 3: Trauma as the main exposure of interest^d
Positive history of trauma	0.94	(0.60–1.48)	0.810	1.13	(0.70–1.83)	0.609
Model 4: Distance from the eye hospital in km as the main exposure of interest^e
0–50 km	1		< 0.0001	1		< 0.0001	1		< 0.0001
50–100 km	1.27	(0.73–2.21)		1.27	(0.73–2.21)		1.26	(0.71–2.21)
100–150 km	2.90	(1.60–5.23)		2.90	(1.60–5.23)		2.63	(1.45–4.80)
> 150 km	5.60	(2.87–10.9)		5.60	(2.87–10.9)		5.06	(2.58–9.92)
Model 5: Distance from nearest health center (for every km increase)^e
Distance from nearest health center (for every km increase)	1.22	(1.05–1.41)	0.007	1.22	(1.05–1.41)	0.007	1.21	(1.05–1.41)	0.09
Model 6: Type of organism^f
No organism detected	1		0.105	1		0.101
Bacteria	1.25	(0.50–3.15)		1.43	(0.55–3.66)
Fungal	1.80	(1.05–3.07)		1.82	(1.06–3.13)
Mixed	2.49	(0.93–6.62)		2.71	(1.07–2.79)

^aAll crude estimates were adjusted for age and sex. ^bUse of TEM was adjusted for age, sex, being a farmer, economic status, education level, distance from the eye hospital, and distance from the nearest health center (n = 298). After adjusting for delay and organism type, the effect of TEM was OR 1.47 95% CI 0.91–2.38, p = 0.11. ^cDelayed presentation was adjusted for age, sex, being a farmer, distance, economic status, education level, TEM, trauma, and previous use of prior treatment before presentation (n = 295). ^dHistory of trauma was a priori based on literature from previous studies. It was adjusted for age, sex, being a farmer, TEM, distance, and prior treatment (n = 306). ^eLong distance from the eye hospital and long distance from the nearest health center were only adjusted for age and sex (n = 309). Their crude and adjusted point estimates are the same. However, the direct effect of distance to eye hospital and distance to nearest health center after adjusting for delay was still highly significant, p < 0.0001 and = 0.009. ^fType of organism was a forced priori and was adjusted for trauma and use of TEM (n = 267).

Figure 3. A DAG framework showing the causal pathways for poor presenting vision. This diagram is adjusted to illustrate the role of TEM. The solid lines indicate hypothesized direct relationships and the dashed lines indicate hypothesized indirect relationships.

Table 6. Factors at presentation predictive of a poor final visual acuity (WHO snellen ordinal scale) at 3 months (n = 260).

Variable	Univariate Analysis			Multivariable Analysis
	Crude OR^a	(95% CI)	p-value	Adjusted OR^b	(95% CI)	p-value
Baseline visual acuity (for every line decrease in vision)	4.78	(3.59–6.35)	< 0.0001	2.98	(2.12–4.19)	< 0.0001
Presence of slough
None	1		0.007
Flat	1.91	(0.95–3.83)
Raised	2.95	(1.46–5.95)
Infiltrate edge being serrated	0.84	(0.58–1.24)	0.393
Satellite lesions being present	0.64	(0.40–1.03)	0.068	0.51	(0.28–0.90)	0.021
Infiltrate color
White	1		< 0.0001
Cream	2.70	(1.56–4.63)
Colored	6.37	(3.10–13.2)
Hypopyon present	2.16	(1.38–3.55)	0.002
Infiltrate size (for every 1 mm increase)	1.60	(1.44–1.79)	< 0.0001	1.19	(1.03–1.36)	0.020
Perforation status at presentation
Not perforated	1		< 0.0001	1		< 0.0001
Impending perforation	11.9	(5.27–26.9)		2.86	(1.11–7.37)
Perforated and sealed	5.60	(1.44–21.8)		1.57	(0.31–7.76)
Perforated	41.0	(17.3–97)		9.93	(3.70–26.6)
HIV status being positive	0.85	(0.39–1.85)	0.683
Diabetes status being positive	0.81	(0.34–1.92)	0.630
Microbiology
No organism detected	1		0.063
Bacteria	1.48	(0.53–4.14)
Fungal	2.25	(1.19–4.26)
Mixed	2.80	(0.86–9.01)

^aAll crude estimates were adjusted for age and sex. ^bFinal predictive model adjusted for age and sex.