Baseline data
A total of 210 participants were enrolled in the study, of which 50 (23.8%) were PWE and 160 (76.2%) PWOE (Table 1). Among the PWE, 32 (64%) were from Msogezi village. The median age of the participants was 31 years (IQR: 15–48) and about half of them were females. The overall prevalence of O. volvulus mf was 49%, and this tended to be higher among PWE (58.0%) compared to PWOE (46.3%), although the difference was not statistically significant (p = 0.195). The prevalence of mf was significantly higher among participants from Mdindo village (64.8%) compared to Msogezi (35.2%), χ2 = 9.57, p = 0.002. The CMFL was also higher in Mdindo village: 3.8mf/mg compared to Msogezi 1.9 mf/mg, z = 3.2, p = 0.001.
Table 1
Characteristics of the study participants before the intake of ivermectin
|
Overall
N = 210
|
PWE
n = 50
|
PWOE
n = 160
|
P value*
|
Socio-demographics
|
|
Age: median (IQR)
|
31 (15–48)
|
30.0 (24.0–39.0)a
|
32.0 (14.0–51.0)b
|
0.544
|
Female gender: n (%)
|
104 (49.5)
|
24 (48.0)
|
80 (50.0)
|
0.872
|
Study village: Mdindo, n(%)
|
74 (35.2)
|
17 (23.0)
|
56 (77.0)
|
0.927
|
Msogezi, n(%)
|
136 (64.8)
|
32 (23.5)
|
104 (76.5)
|
Anthropometrics
|
|
Height in cm: median (IQR)
|
152.0 (140.0-159.0)
|
152.5 (143.0–156.8)
|
152.0 (139.9–160.0)
|
0.765
|
Body mass index
|
19.6 (17.1–22.1)
|
20.4 (18.4–22.0)
|
19.5 (16.9–22.4)
|
0.380
|
Weight in Kg: median (IQR)
|
46.0 (37.3–53.0)
|
46.0 (40.3–52.0)
|
46.8 (34.8–53.1)
|
0.966
|
Onchocerciasis
|
|
Positive skin snip: n (%)
|
103 (49.0)
|
29 (58.0)
|
74 (46.3)
|
0.195
|
Pre-IVM mf density for all participants: median (IQR)
|
0.0 (0.0-2.7)
|
0.6 (0.0–4.4)
|
0.0 (0.0–1.9)
|
0.315
|
Pre-IVM mf density for participants with positive skin snip: median (IQR)
|
3.6 (1.7–13.3)
|
3.0 (1.7–11.3)
|
4.24 (1.7–15.6)
|
0.886
|
Palpable nodules: n (%)
|
19 (9.0)
|
8 (16.0)
|
11 (6.9)
|
0.085
|
Itching: n (%)
|
51 (32.1)
|
9 (24.3)
|
42 (34.4)
|
0.316
|
Ivermectin use in 2018: n (%)
|
159 (75.7)
|
37 (74.0)
|
118 (75.6)
|
0.706
|
a1 missing observation; b7 missing observations; IQR: interquartile range, mf: Microfilarial; IVM: ivermectin, NA: Not applicable; *Mann Whitney U test for continuous variables, Chi-squared test for categorical variables (Fisher exact test if expected values < 5) |
The proportion of individuals with positive skin snips increased with increasing age, χ2trend = 4.29, p = 0.038. However, the proportion of positive skin snips in the youngest age group (6–11 years) was slightly higher (41.7%, 95%CI: 24.8–58.6) than in the subsequent age group (33.3%, 95%CI: 13.0-53.7), Fig. 1.
Effect of ivermectin on mf density among O. volvulus infected PWOE and PWE
Of the 210 study participants examined at baseline, 163 (77.6%) were available for a follow-up skin snip sample three months post-ivermectin. The main reasons for not participating in the post-ivermectin skin snip testing included refusal due to discomfort caused by the initial skin snipping, and being away from the study villages during the second skin snipping period. Of the 163 participants with a follow up skin snip sample, 76 (46.6%) had a positive skin snip at baseline compared to 29 (17.8%) post-ivermectin, p < 0.001. The proportion of individuals who took ivermectin during the 2018 CDTI increased significantly from 75.5%z at the baseline survey to 92.0% during the post ivermectin survey, (Mcnemar’s-ꭕ2 = 18.7, p < 0.001), (Table 2). Considering only PWOE and PWE who took ivermectin treatment, > 80% decrease in mf density was observed in 54/66 (81.8% [95% CI: 72.3–91.4]) participants who were infected at baseline. However, only 14 out of 19 PWE (73.7% [51.9–95.5]) attained the threshold of > 80% decrease in mf density. There was no difference in frequency of seizures at baseline and post ivermectin, p = 0.480 (Table 2).
Table 2
Response of ivermectin on mf density in all 163 participants with both baseline and three months post-ivermectin skin snip results
|
Skin snip survey
|
|
Characteristics
|
Baseline
|
Post-ivermectin
|
P-value
|
All participants (n = 163)
|
Took ivermectin in previous CDTI round, n (%)
|
123 (75.5)
|
150 (92.0)
|
< 0.001 a
|
Positive skin snips: n (%)
|
76 (46.6)
|
29 (17.8)
|
< 0.001 a
|
Mf density: median (IQR)
|
0.0 (0.0-2.8)
|
0.0 (0.0–0.0)
|
< 0.001 b
|
Mf density: mean (95%CI), n = 162
|
1.45 (0.98–2.04)
|
0.23 (0.11–0.37)
|
< 0.001
|
> 80% reduction in mf density (only for participants with positive skin snip at baseline): n (% [95% CI])
|
NA
|
54/66 (81.8 [72.3–91.4])c
|
NA
|
PWE only (n = 42)
|
Positive skin snips: n (%)
|
22 (52.4)
|
13 (30.9)
|
0.020 a
|
Mf density: median (IQR)
|
0.26 (0.0-3.78)
|
0.0 (0.0-0.23)
|
< 0.001 b
|
Mf density: mean (95%CI)
|
1.73 (0.76–3.24)
|
0.22 (0.07–0.40)
|
< 0.001
|
> 80% reduction in mf density (only for PWE with positive skin snip at baseline): n (% [95% CI])
|
NA
|
14/19 (73.7 [51.9–95.5])d
|
NA
|
Experienced a seizure in the last week, n (%)
|
8/32 (25)e
|
10/32 (31.2)e
|
0.480a
|
Seizures per month: median (IQR)
|
0.0 (0.0–2.0)
|
0.0 (0.0-0.5)
|
0.241b
|
aMcnemar’s test, bWilcoxon signed-rank test ,c10 missing observations post-ivermectin, d3 missing observations, e10 missing observations post-ivermectin IQR = interquartile range, Mf = microfilarial |
Overall, the geometric mean mf density decreased from 1.45 mf/mg (95% CI: 0.98–2.04) at baseline to 0.23 mf/mg (95% CI: 0.11–0.37) 3 months post-ivermectin, p < 0.001. Majority (71.0%) of 76 people who tested skin snip positive at baseline tested negative three months post-ivermectin, while among those who had negative skin snips (n = 87), 7 (8.0%) of them tested positive three months post the ivermectin, giving an OR of 7.71 (95%CI: 3.50–20.10), McNemar's P < 0.001.
Skin snips positivity rate among PWE decreased from 52.4% (22/42 PWE) at baseline to 30.9% (13/42 PWE) three months post ivermectin; p = 0.020. Of the 22 PWE who were positive at baseline, 12 (54.5%) had no detectable mf in their skin snips post-ivermectin, while only 3 (15%) out of 20 PWE with no mf detected at baseline were detected with mf post-ivermectin, giving an OR of 4.0 (95%CI: 1.08–22.09), McNemar's p = 0.020.
Although in univariate analysis, three factors (being a PWE, village of residence and pre-ivermectin mf density) were found to be associated with persistence of mf three months post ivermectin treatment, in multivariate analysis only being a PWE (OR = 2.65, p = 0.033) and pre-ivermectin mf density (OR = 1.54, p = 0.003) remained significant (Table 3). Self-reported history of ivermectin use during the past years was not associated with skin snip positivity following ivermectin treatment in this study.
Table 3
Factors associated with positive skin snips three months post-ivermectin
Covariates
|
Univariate
|
Multivariate
|
|
OR (95%CI)
|
P-value
|
OR (95%CI)
|
P-value
|
Sex (Female)
|
0.95 (0.43–2.12)
|
0.902
|
|
|
Age (in years)
|
1.00 (0.98–1.02)
|
0.675
|
|
|
Being a PWE
|
2.56 (1.10–5.95)
|
0.030
|
2.65 (1.08–6.51)
|
0.033
|
Village of residence: Mdindo
|
1
|
|
|
|
Msogezi
|
0.43 (0.19–0.96)
|
0.040
|
0.59 (0.24–1.45)
|
0.249
|
BMI – Normal or overweight (≥ 18.5)
|
1
|
|
|
|
– Underweight (< 18.5)
|
0.80 (0.35–1.80)
|
0.582
|
|
|
Pre-ivermectin mf density*
|
1.62 (1.24–2.11)
|
< 0.001
|
1.54 (1.16-.03)
|
0.003
|
Never used ivermectin
|
1.07 (0.29–4.04)
|
0.916
|
|
|
Did not take ivermectin in 2018 (most recent CDTI before this study)
|
1.61 (0.48–5.41)
|
0.439
|
|
|
*Log-transformed
|
The mf density at three months post-treatment ranged from 0.0 to 100 mf/mg. In a univariate negative binomial regression model, both higher pre-ivermectin mf-density (IR = 1.77, 95% CI: 1.27–2.46, p = 0.001) and village of residence (Msogezi village; IR = 0.33, 95%CI: 0.12–0.91, p = 0.032) were the variables significantly associated with mf density three months after ivermectin treatment. However in the multivariate model, only pre-ivermectin mf-density remained significant (IR = 1.65, 95%CI: 1.18–2.31, p = 0.003), (Table 4).