Onchocerciasis is not a major cause of blindness in two endemic villages in Sierra Leone

Abstract

Objective

Sierra Leone, a country where onchocerciasis is endemic in 14 of the 16 districts, was the focus of our investigation. Despite 17 rounds of annual ivermectin treatment since 2005, a report circulated by a local politician indicated an increase in cases of suspected onchocerciasis-related vision impairment in two villages (Mangobo and Petifu) in Tonkolili district. In response, the National Neglected Tropical Disease Program conducted a comprehensive investigation. Ophthalmological, parasitological, and serological tests were conducted using standard procedures to determine the relationship between self-reported vision loss and onchocerciasis in adults. In addition, serological tests were carried out on children aged 5 to 9 years to assess the recent status of exposure to onchocerciasis in the two villages.

Results

Reported vision loss in 37 patients was mainly due to cataracts (35.1%), allergic conjunctivitis (18.9%), refractive error (10.8%), and other conditions not related to onchocerciasis. There were 40.7% of all adults (N = 54) tested and 29.0% of 31 persons with self-reported vision loss who were positive for Ov-16 IgG4 antibodies, suggesting a history of exposure to onchocerciasis. However, otoscopic eye examinations and microscopic skin snip tests were all negative for Onchocerca volvulus microfilariae, indicating no active or low-intensity infection among adults and a low or zero risk of serious ocular morbidity in the two villages. Onchocerciasis may no longer be a major cause of blindness in these two villages. Apparently, 4.6% of 153 children aged 5 to 9 years tested positive for Ov-16 IgG4 antibodies, suggesting that onchocerciasis transmission is likely still ongoing in the two villages. The data presented here suggest that more annual rounds of mass treatment with ivermectin with high coverage are needed to eliminate onchocerciasis transmission in this area.

Introduction

Onchocerciasis, or river blindness, is caused by infection with Onchocerca volvulus, transmitted by Simulium blackflies. It is a leading infectious cause of blindness and skin disease. The global objective is to eliminate the transmission of onchocerciasis through regular treatment of all at-risk populations with ivermectin [1]. The disease is endemic throughout Sierra Leone, with the exception of the capital, Freetown, and the island of Bonthe [2, 3]. The country was part of the Onchocerciasis Control Program for West Africa from 1998 to 2002 [4] and the African Program for Onchocerciasis Control from 2003 to 2007 [5]. Baseline surveys, using skin snip biopsy and microscopic examination to detect microfilariae (mf), showed that 88% of villages were either meso- or hyper-endemic (prevalence range: 47-88.5%) [4]. Onchocerciasis accounted for approximately 30% of all blindness in the country after cataracts, with some areas, such as the Taia river basin, having onchocerciasis blindness rates as high as 5.9% [4, 6, 7]. Vector control and ivermectin treatment were severely disrupted by the civil war from 1991 to 2002 [8]. The situation improved by 2005 but was interrupted again in 2014 by an outbreak of Ebola virus disease [3]. Impact assessments in 2010 after five rounds of ivermectin treatment using skin snip biopsy and in 2017 after six further rounds of treatment using the Ov-16 serological rapid diagnostic tests (RDTs) suggested that Sierra Leone was on track to achieve onchocerciasis elimination [2, 3]. Since 2017, six more rounds of mass treatment with ivermectin have been conducted by 2023.

In February 2023, a video of a local politician began circulating via email, suggesting a resurgence of cases of onchocerciasis blindness in two villages: Mangobo and Petifu in the Yoni Mamaila chiefdom of Tonkolili district in central Sierra Leone. In mid-February, the National Neglected Tropical Disease Program (NNTDP) attended a community meeting to gather more information. Residents reported more than 30 people with vision loss and an increasing blackfly nuisance in these villages. They also confirmed that the community health workers regularly distributed ivermectin and that communities were regularly participating in mass drug administration. In total, Tonkolili district as a whole had received 17 (16 effective) rounds of mass treatment with ivermectin since 2005 with effective coverage (≥ 65% epidemiological coverage) (Fig. 1).

Fig. 1

Reported treatment coverage from 2005 to 2022 in Tonkolili district, Sierra Leone

In early September 2023, the NNTDP conducted ophthalmological, parasitological, and serological investigations in the two villages. The objective was to investigate whether self-reported cases of visual impairment were onchocerciasis-related and to assess the current status of onchocerciasis transmission in these villages. This paper reports the findings and discusses the challenge of onchocerciasis elimination in Sierra Leone.

Methods

Study area and design

Mangobo is located along the Taia Riverbank, and Petifu is located about 3 km west of the river in the Yoni Mamaila chiefdom of Tonkolili district. The area is bordered to the west and east by Moyamba district (Fig. 2). These are hard-to-reach communities with a population of 322 in Mangobo and 789 in Petifu. These two villages had never been surveyed for onchocerciasis prevalence prior to this investigation, but are located in a meso-endemic zone at baseline [2, 3]. The area is upstream of the hyper-endemic Taia River basin in Mayamba district, where mf prevalence was 29.7–88.5% prior to the control intervention [9]. This was a cross-sectional investigation with convenience sampling of participants.

Fig. 2

Geographical locations of Mangobo and Petifu villages in Tonkolili district of Sierra Leone. World Imagery basemap source: Esri, Maxar, GeoEye, Earthstar Geographics, CNES/Arbus DS, USDA, USGS, AeroGRID, IGN, and the GIS User Community

Ophthalmological examination

Village chiefs and community health workers mobilized both communities before the investigation team arrived. A community meeting was held, and residents who had self-reported vision loss were invited to participate in the examination, while some others volunteered for an eye examination. Two ophthalmologists from the National Eye Health Program in Bombali and Tonkolili districts conducted eye examinations to diagnose eye conditions and to detect mf in the anterior chamber of the eyes using a hand-held otoscope according to standard procedures [10]. Eye conditions and ocular mf findings for each patient were recorded on paper.

Parasitological examination

All individuals examined for eye conditions were asked to provide skin snip samples by skin snip biopsy to detect mf for Onchocerca volvulus infection. Thirty-four individuals gave verbal consent to provide skin snip samples. Two skin biopsies were taken from the right and left iliac crest of each volunteer. A sterilised 2 mm Holth corneoscleral punch was used to obtain the two bloodless skin snip biopsies. The skin snip samples were placed in normal saline for 24 h and then examined under a light microscope for O. volvulus microfilariae [11].

Serological examination

Volunteers undergoing ocular examinations also provided blood samples. Dried blood spot (DBS) samples were collected by finger prick for serological testing for the presence of Ov-16 IgG4 antibodies, an indicator of O. volvulus exposure. In addition, to assess the current situation of onchocerciasis transmission in the two villages, children aged 5–9 years were tested for Ov-16 IgG4 antibodies, as the presence of such antibodies in this group of children represents recent exposure and active infection [12], and WHO recommends testing this group of children for transmission assessment [13,14,15]. All children aged 5–9 years in the two villages were invited to participate. Those who volunteered were recruited, and DBS samples were collected from them. The DBS samples were then packed and transported according to standard protocols to the Central Public Health Reference Laboratory in Freetown for analysis [15]. DBS samples were eluted overnight at the laboratory and tested using Bioline Onchocerciasis IgG4 tests (Ov-16 RDT, Abbott Rapid Diagnostics, South Korea) to detect Ov-16 IgG4 antibodies per the manufacturer’s instructions [15]. The final results were read and recorded after 24 h of incubation [16].

Data analysis

The results were entered into an Excel spreadsheet. Descriptive analysis and chi-squared test were used to compare the positivity rate between groups using SPSS statistics (IBM, version 23). The geolocation map of the two villages was created using ArcGIS version 10.8.2 (ESRI, Redlands, California, United States).

Results

Eye examination and O. volvulus infection in adults

Thirty-seven (37) persons aged 12 to 75 years (mean age: 51.4 years, standard deviation: 15.1 years) who reported vision loss presented themselves and were examined by ophthalmologists. Various eye conditions were diagnosed, as shown in Fig. 3. Of 37 persons, the main eye conditions were cataracts (35.1%), allergic conjunctivitis (18.9%), refractive error (10.8%), and other eye conditions. Five people had normal eyes, and two reported dimmed vision with inconclusive diagnosis. In addition, one case of blindness in a 60-year-old man may have been caused by O. volvulus due to suspected uveitis, optic atrophy, and punctate keratitis. No mf was observed in the anterior chamber of any of the patients examined. Individuals with ocular morbidity were referred to the eye health program for management.

Fig. 3

Number of eye conditions observed in the 37 volunteers who self-reported vision loss. * One case suspected of onchocerciasis-related blindness

Of the thirty-seven (37) adults who self-reported vision loss and were examined for eye conditions and anterior chamber mf, 18 (48.6%) persons aged 35–80 years were examined for O. volvulus mf by skin snip biopsy. In addition, 16 other community members who did not report vision loss also volunteered for skin snip biopsy. None of these 34 adults tested were reported to be positive for mf (Table 1). This was not a community-wide survey, so the community microfilarial load (CMFL) was not calculated.

Table 1 Results of skin snip biopsy in adults in the two villages (Mangobo and Petifu)

Blood samples were collected from a total of 54 adults, including 31 (83.8%) of 37 who self-reported and were examined for eye conditions and 23 other community members who did not report vision loss (Table 2). Among the 31 patients, 9 were positive for Ov-16 IgG4 antibodies by Ov-16 RDT, with a positivity rate of 29.0% (95% CI: 13.1–45.0%). This was significantly lower than the positivity rate for Ov-16 IgG4 antibodies of 56.5% (95% CI: 36.3–76.8) in the other 23 residents who did not report vision loss (χ² = 4.133, p = 0.042). Among all subjects, the positivity rate was significantly higher in male adults, 55.6% (95% CI: 36.8–74.3%), than in female adults, 25.9% (95% CI: 9.4–42.3%) (χ² = 4.909, p = 0.027). There was no statistically significant difference in Ov-16 antibody prevalence between age groups (χ² = 1.72, p = 0.190).

A subset of 17 patients with self-reported vision loss underwent ophthalmic examination, skin snip biopsy, and serological testing by Ov-16 RDT. No mf was found in the anterior chamber or skin snip biopsy, and five of 17 patients were positive for Ov-16 IgG4 antibodies, 29.4% (95% CI: 7.8–51.1%). The single case of blindness probably related to onchocerciasis was both mf and serologically negative.

O. volvulus infection in children

A total of 182 children from two villages voluntarily provided blood samples, including 153 children aged 5–9 years: 19 from Mangobo and 134 from Petifu (Table 2). Twenty-nine (29) children aged 10–13 years were excluded from the analysis. Of the 153 children aged 5–9 years, 7 were positive for Ov-16 IgG4 antibodies (4.6%, 95% CI: 1.3–7.9%). The positivity rate of Ov-16 IgG4 antibodies was similar in boys at 5.9% (95% CI: 0.3–11.5%) and girls at 3.5% (95% CI: 0-7.5%) (χ² = 0.479, p = 0.489). Seropositivity for Ov-16 IgG4 antibodies in children aged 5–9 years by village was 5.2% (95% CI: 1.5–9.0%) in Petifu and 0% in Mangobo (χ² = 1.040, p = 0.308).

Table 2 Results of Ov-16 RDT tests in the two villages (Mangobo and Petifu)

Discussion

Eye examination revealed that self-reported vision loss in the two villages was mainly due to cataracts, ocular allergy, refractive error, and other non-onchocerciasis eye conditions, with cataracts remaining the most common cause of blindness. This was consistent with previous findings in Sierra Leone [17]. Twenty-two adults, 29.0% of those with self-reported vision loss and 56.5% of other community volunteers, tested positive for Ov-16 IgG4 antibodies, indicating likely exposure to O. volvulus infection during their lifetime, possibly in their residential villages. The absence of skin and/or ocular mf in these individuals suggests either no active infections or very low-intensity infections. Blindness caused by onchocerciasis is directly related to the microfilarial load [18] and is predicted in communities with a mf prevalence of ≥ 40% and a community microfilarial load (CMFL) of ≥ 5 mf/skin snip [19, 20]. Annual ivermectin treatment sharply reduces the incidence of blindness after two years of mass treatment with ivermectin [21]. The current situation of no or very low-intensity infections in these villages poses a low or zero risk of serious new ocular morbidity. The first large-scale ivermectin mass treatment in endemic villages in the Taia river basin started in 1990 [22]. A study of patients at an eye hospital patients in 1992 showed that onchocerciasis blindness was estimated to be 15% of all blindness, a reduction from 30% before 1990 [6]. More recently, a rapid assessment of avoidable blindness in Siera Leone in 2021 showed that the main causes of blindness were cataracts, glaucoma, other corneal opacities, and other eye conditions, and that no cases of blindness found were attributed to onchocerciasis in the populations surveyed [17]. Therefore, after many years of intervention, onchocerciasis may no longer be a significant cause of blindness in these villages.

The results from children aged 5–9 years showing 4.6% seropositivity with Ov-16 IgG4 antibodies seem to indicate a recent exposure to O.volvulus infection. This is possibly an indication of continuing transmission of O.volvulus. However, recent exposure does not necessarily indicate that transmission is ongoing. Entomological information on blackfly infectivity would help to confirm the likely continuing transmission of O.volvulus infection in these two villages. This would validate the decision to continue mass treatment with ivermectin to eliminate onchocerciasis in Tonkolili district. The 2010 national impact assessment suggested good progress in mf prevalence reduction from 60.4 to 16.1% in Tonkolili district [2]; however, it was still one of the areas with the highest Ov-16 antibody prevalence (2.5%) in the country in 2017 [3]. The duration of ivermectin treatment required to achieve onchocerciasis elimination depends on the baseline endemicity levels, the force of infection, an inadequate strategy, or the quality of mass treatment [23, 24]. The two villages are located in an area with meso-endemicity at baseline, and the current seroprevalence of 4.6% by Ov-16 IgG4 antibodies is in line with the predicted mf prevalence after 16 years of treatment in Africa for hypo- to meso-endemic areas [21].

Together with program information across the country, it is recommended that the NNTDP continue at least annual mass treatment with ivermectin and ensure effective treatment coverage in all endemic communities by taking extra measures to improve program quality. This will help achieve the national goal of eliminating onchocerciasis transmission.

Limitations

The investigation focused on the community members who self-reported vision loss to confirm whether these were onchocerciasis-related. Participation was voluntary and the results may not be representative of all the community members who may have vision impairment either due to onchocerciasis or other eye conditions. The sample size for mf by skin snip was relatively small and not from the wider community. The mf results may not be representative of the true situation in the population in the two villages. However, the relatively low prevalence of Ov-16 IgG4 antibodies in children aged 5–9 years suggests that the level of transmission in the two villages is relatively low, although we did not conduct an entomological investigation to confirm this.