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Journal of Ophthalmology of Eastern Central and Southern Africa July 2014

Blinding Onchocerciasis in Pader District, Northern Uganda Watmon B1, Lakwo TL2, Onapa AW3

1Consultant Ophthalmologist, Gulu Regional Referral Hospital, Uganda 2National Onchocerciasis Control Programme Manager, Ministry of Health, Uganda 3Programme Manager, ENVISION/RTI NTD Control, Kampala, Uganda Corresponding author: Dr B Watmon. Email: [email protected] ABSTRACT

Background: Onchocerciasis is caused by a filarial nematode Onchocerca volvulus, and is transmitted by a female black fly of the genus Simulium which breeds in fast flowing rivers. In Uganda, the disease is endemic in 37 districts with clinical manifestations mainly on the skin. The long-term armed conflict in northern Uganda made research and control of onchocerciasis in the region and particularly Pader district receive little attention. There have been no attempts to establish the magnitude of the disease in the region.Objective: To establish the magnitude and clinical manifestations of Onchocerciasis in Pader district, northern Uganda.Methods: Twenty parishes in sub counties with Rapid Epidemiological Mapping of Onchocerciasis (REMO) nodule prevalence of 25.0% or more were randomly sampled and 675 persons consecutively enrolled in 13 parishes. The respondents underwent dermatological, parasitological and ocular examinations.Results: A total of 675 persons were examined and of these, 318 had skin snipping and microscopy done. The prevalence of microfilaria (mf) in skin snip was 29.6% (95% CI: 24.6%-34.6%) while prevalence of nodules was 30.1% (95% CI: 3.1%-6.5%). The prevalence of microfilaria in the anterior chamber of the eye (MFAC) was 4.1% (95% CI: 2.6%-5.6%) and that of reversible ocular lesions was 4.0% (95% CI: 2.5%-5.5%). The reversible ocular lesions of onchocerciasis observed were punctate keratitis stage B (PKB, 0.1%), punctate keratitis stage D (PKD, 0.1%) and punctate keratitis stage E (PKE, 3.7%) while the irreversible ocular lesions were observed in 16.1% (95% CI: 13.3%-18.9%) of the respondents. The most important irreversible lesions were optic atrophy 6.4%, (95% CI: 3.7%-9.1%) and sclerosing keratitis, 5.2% (95% CI: 2.8%-7.6%). Visual impairment was detected in 29.2% (95% CI: 25.8%-32.6%) of the respondents and the main causes were cataracts (27.4%) and optic atrophy (21.8%). The association between irreversible lesion and visual loss (p< 0.00) and irreversible lesions and nodules (p< 0.00) were both significant. Conclusion: This study indicates that the onchocerciasis in Pader district is the blinding type. There is need to strengthen health education, community social mobilization and start biannual Mass Drug Administration (MDA) with Ivermectin.

Republic of Congo, Northern Uganda, West Nile and the Elgon Mountain regions. A study conducted by Ndyomugyenyi in 1992 indicated that over 3 million people in Uganda were at risk of infection and 1.4 million were infected2. In the 1990s the National Onchocerciasis Control Programme of the Ministry of Health (Uganda) started control projects in most of the endemic districts using MDA with Ivermectin. Kitgum and Pader were not included on the control program because of the prolonged insurgency in northern Uganda until after the Rapid Epidemiological Mapping of Onchocerciasis (REMO) in 2008. Information on ocular manifestations of onchocerciasis in northern Uganda had been limited to clinical reports from the Eye Department of Gulu Regional Referral Hospital3. These results provide baseline data for future evaluation of any onchocerciasis control program in the district.

INTRODUCTION

Onchocerciasis is caused by a filarial nematode Onchocerca volvulus and transmitted by the female black fly, Simulium, which breeds in fast flowing rivers, hence the name river blindness. The disease is endemic in large areas of Africa where favorable ecology for the black fly that is a determinant of disease distribution prevails and is known for both ocular and dermatological effects. In the affected communities the most devastating ocular complication is blindness. It has been reported that mortality amongst the blind people is four times higher than in the sighted persons of the same age in the community1.

In Uganda the disease is endemic in 37 of the 112 districts which include the areas located in the western axis of the country bordering the Democratic

East African Journal of Ophthalmology July 2013

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The aim of the study was to establish the magnitude and ocular manifestations of onchocerciasis in Pader district, northern Uganda and objectives were to determine the prevalence of onchocercal nodules, microfilaria in the anterior chamber of the eye, the reversible and irreversible ocular manifestations of onchocerciasis.

MATERIALS AND METHODS

This survey was conducted in Pader district in northern Uganda during the period January to August 2009. At the time of the survey Pader had two counties; Aruu and Agago. This study was done in Aruu County which had nine sub counties and 35 parishes. The sample size was calculated using Kish and Frankel formula4. Multistage cluster sampling method was employed based on the REMO survey report of 2008 from the Ministry of Health National Onchocerciasis Control Programme5, 6. Seven sub counties with nodule prevalence more than 25.0% were sampled. In each sub county, parishes were randomly sampled basing on probability proportionate to population. Sixty individuals aged five years or more were consecutively recruited until the sample size of sixty per parish was reached. Participants were examined from a common site which was either a primary school or health facility.

The study variables included age, sex, intake of Ivermectin, presence of onchocercal nodules and skin snip for analysis for microfilaria. The ocular variables were visual acuity, evidence of microfilaria in the cornea, onchocercal related keratitis, presence of microfilaria in the anterior chamber, evidence of the iritis and lesions in the posterior segment of the eye.

Communities were mobilized through their leaders, local radio announcements and telephone calls to Village Health Teams. Prior to enrolment, health education focusing on onchocerciasis and other neglected tropical diseases were given to the gathering. The study purpose and procedures were explained and consent sought. Parents or next of kin consented for the minors.

Each participant was given an identification number prior to examination; visual acuity assessed using the Snellen chart or appropriate method depending on the level of visual impairment and age7. Ocular examinations were done with torch, direct ophthalmoscope and hand held portable Slit Lamp at x10 magnification. Dermatological and nodule examinations were done while skin snip for microscopy was conducted under standard aseptic procedure. Respondents who had other significant medical conditions were either treated or referred for further management in the appropriate health facility. Skin snip slides were preserved under standard conditions and analyzed by the Vector Control Officers.

Data was collected by the Ophthalmologist, Ophthalmic Clinical and Vector Control Officers using pre-tested closed ended questionnaires, cleaned and entered in Excel and exported to SPSS 16.0 for analysis.

Ethical clearance and permission to conduct the survey was obtained from Uganda National Council of Science and Technology, the district authority and community leaders. Informed consent was obtained from the individual participant or the next of kin of the children. The procedures of taking skin snip for examinations and associated complications or pain were explained to participants in groups and thereafter individually. Only those adults or children whose parents or next of kin consented had skin snip done.

RESULTS

Demographic characteristics: A total of 675 persons were examined in the 13 surveyed parishes: females 351(52.0%) and males 324 (48.0%). The distribution of the respondents by age was as follows: 5-14 years 203(30.1%), 15-24 years 96(14.2%), 25-34 years 76 (11.3%), 35-44 years 94 (13.9%), 45-54 years 69 (10.2%), 55-64 years 59(8.7%) and above 64 years 78(11.6%).Intake of Ivermectin: Sixty one percent of the respondents had swallowed Ivermectin in the previous 12 months; males 335 (49.6%) and females 340 (50.4%). The majority (83.5%) received Ivermectin from the VHT in their respective village of stay, 15.7% from the health facility and remaining 0.7% received from the District Vector Control Officer. Intake of Ivermectin was lowest in the age group 25-34 years (46.0 %).Nodules: Of the 675 participants 203 (30.1%, 95% CI: 3.1%-6.5%) had palpable onchocercal nodules in the following sites: Iliac region (50.9%), buttocks/coccyx (25.5%), chest (12.4%), head (5.0%), knee (4.7%) and elbow (0.7%). The youngest with nodules were two nine year old males (Table 1). The youngest with nodules were two nine year old males.

Table 1: Statistical relationship between nodule site and visual loss among participants (n=675)

Nodule site

Chi-square Df P-value 95% CI

Head 26.101 3 0.00 5.0% (2.0%-8%)Chest 13.925 3 0.00 12.4%, (8.0-17.5%)Iliac crest 49.019 3 0.00 50.9% (44.0-57.8%)Buttocks / coccyx 54.592 3 0.00 25.5 % (20.0-32.0%)

Knee 7.921 3 0.05 4.7 % (1.8%-7.6%)Elbow 9.228 3 0.03

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Skin snip and microfilaria in the anterior chamber: Of the 318 respondents who had skin snip taken for microscopic examination for O.vulvulus microfilaria, 94 (29.6%, 95% CI: 24.6%-34.6%) were positive. Twenty eight (4.1%, 95% CI: 2.6%-5.6%) of the 675 respondents had Microfilaria in the Anterior Chamber (MFAC) of the eye (Figure 1).

Figure 1: Distribution of positive skin snip and microfilaria in anterior chamber by age

28

3

12

5-14 15-24(years)

25-34 35-44 45-54 55-64 >65

75 6

14

4

8

3 3

7

2

20

Pos SnipMFAC

The youngest with a positive snip were two five year olds (male and female). Both positive skin snip and presence of MFAC were statistically significantly associated with visual loss [(p< 0.00) and (p64

Blind Bilateral

Blind Unilateral

Bilateral SVI

Unilateral SVI

Reversible ocular lesions: Reversible anterior segment lesions, Puntate Keratitis was observed in 27 (4.0%, 95% CI: 2.5%-5.5%) (Table 2).

Table 2: Distribution of reversible ocular lesionsReversible lesion Frequency (%)Punctuate Keratitis stage B (PKB) 1 0.1

Punctuate Keratitis stage D (PKD) 1 0.1

Punctuate Keratitis stage E (PKE) 25 3.7(CI: 2.3-5.1%)

Punctuate Keratitis stage F (PKF); normal cornea

638 94.5(CI: 92.8-96.2)

Active iritis 2 0.3

Total 668 98.8

In eight cases (1.2%) there were corneal scars and hence the anterior segment could not be well evaluated. Presence of live microfilaria coiled in the cornea [PKA] and inflammatory reactions around the dead microfilariae in the cornea [PKC] were not observed. Irreversible ocular lesions: A total of 109 (16.1%, 95% CI: 13.3%-18.9%)) respondents had irreversible ocular lesions (Table 3).

Table 3: Distribution of irreversible ocular lesions (n=109)Age

group Sclerosing

Keratitis(SK)Iris

atrophyOptic

Atrophy(OA)Optic

Neuritis Chorioretinitis Total

5 - 14 3(33.3%) 0(0.0%) 5(55.6%) 0(0.0%) 1(11.1%) 9(8.3%)15 - 24 5(26.3%) 2(10.5%) 8(42.1%) 1(5.9%) 1(5.9%) 17(15.6%)25 - 34 4(36.4%) 3(27.3%) 4(36.4%) 0(0.0%) 0(0.0%) 11(10.1%)35 - 44 1(7.1%) 4(28.6%) 5(35.7%) 2(14.3%) 2(14.3%) 14(12.8%)45 - 54 11(50.0%) 3(13.6%) 6(27.3%) 0(0.0%) 2(9.1%) 22(20.2%)55 - 64 4(23.5%) 4(23.5%) 8(47.1%) 0(0.0%) 1(5.9%) 17(17.6%)> 64 7(36.8%) 5(26.3%) 7(36.8%) 0(0.0%) 0(0.0%) 19(17.4%)Total 35(32.1%) 21(19.3%) 43(39.4) 3(2.8%) 7(6.4%) 109(100%)


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CONTACT DETAILSMS Aparna Patel

Territory Manager-East Africa Alcon LabsCell No: 0722 514 044

Email: [email protected]


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The overall prevalence of optic atrophy and sclerosing keratitis in the surveyed group was 6.4% (95% CI: 3.7%-9.1%) and 5.2% (95% CI: 2.8%-7.6%) respectively. Of the 43 respondents with optic atrophy, 24 (55.8%) had positive skin snips. Occurrence of irreversible lesions was significantly associated with positive skin snip, (x2 = 400.982; df = 205, p = 0.00) (Figure 3). Figure 3: Distribution of sclerosing keratitis and optic atrophy by age

Distribution of Sclerosing Keratitis and Optic Atrophy

0

2

4

6

8

10

12

5 - 14 15 - 24 25 - 34 35 - 44 45 - 54 55 - 64 > 65

Age group

Freq

uenc

y

S.KO.A

A total of 85 eyes had optic atrophy, three were unilateral and forty cases were bilateral and 54.0% were blind in terms of visual acuity. There was significant association between occurrence of these irreversible ocular lesions with visual loss (x2 = 188.454, df=15, p-value 0.00). Causes of visual impairment: Of the 675 respondents 197 (29.2%, 95% CI: 25.8%-32.6%) had visual impairment in one or both eyes with the main causes being cataract (27.4%), optic atrophy (21.8%), corneal scars (18.3%) and maculopathy (12.7%).

Table 4: Causes of visual impairment amongst the respondents

Disorder Monocular (n=64)

Binocular (n=133)

Total (n=197)

Corneal opacities 16 (8.1%) 20(10.2%) 36(18.3%)Cataract 23(11.7%) 31(15.7%) 54(27.4%)Optic atrophy 3(1.5%) 40(20.3%) 43(21.8%)Maculopathy 5(2.5%) 20(10.2%) 25(12.7%)Chorioretinopathy 2(1.0%) 13(6.6%) 15(7.6%)Others 15(7.6%) 9(4.6%) 24(12.2%)Total 64(32.5%) 133(67.5%) 197(100%)

The most affected age group were those aged above 55 years. The majority of the respondents with optic atrophy were below 45 years and 24 of them had positive skin snip.

DISCUSSION

The results of clinical, parasitological and ocular examinations in this study reveal the presence of onchocerciasis in the district. Intake of Ivermectin: The 61.0% intake of Ivermectin was lower than WHO recommended annual coverage of 65% 1. Katabarwa et al8 reported treatment coverage

in the following places: Bangange (Cameroon) 99.5%; Kasese (Uganda) 88%; Nebbi (Uganda) 91%. This low coverage could be due to the fact that community distribution of Ivermectin in Pader was still a new program which was not yet fully established since it started one year prior to this study. Nodules: The distribution of onchoceral nodules at the different sites nearly doubles that reported by Fischer et al9 amongst the community in Kabarole district in Uganda which was as follows: Iliac crest 27.9%, buttocks 11.3% and chest 5.3%. Lakwo et al 6 reported nodule prevalence of 24% in Pader district while Krupp and Chatton10 reported that nodules are mostly seen over bony prominences like the iliac crest, coccyx, trochanter, chest wall and limps. In this survey nodules located in the head, chest, iliac region and buttocks were all separately statistically significantly associated with visual loss [(x2 = 26.101 df= 3; p-value 0.000), (x2 =13.925; df= 3 p-value 0.003), x2 = 49.019; df= 3; p-value 0.000) and (x2 = 54.592; df= 3; p-value 0.000) respectively].

We observed that children with nodules in the head tend to develop visual impairment earlier than their counter parts with nodules elsewhere. There was no significant association of nodules in the knees and elbows with visual loss.Skin snip: Positive skin snip confirmed the presence of onchocerciasis in Pader and a prevalence of 29.6% shows high endemicity. In the younger age groups 5-24 years positive snip was higher in males compared to females while in the age groups 25-64 years more females than males had positive snips. This could probably be due to young males (5-24 years) being more involved in outdoor activities such as swimming, fishing charcoal burning and farming compared to their counterparts in the same age bracket. In the groups above 24 years females tend to be more involved in outdoor activities such as gardening, gathering fire woods and fetching water hence increasing exposure to the fly bites. In this community, weeding of crops is essentially the work of women. Majority of the men dig/ plough in the morning and retire home by midday while women may continue up to late afternoon or evening hours. Reversible ocular lesions: The occurrence of reversible lesions of 4% was low compared to the findings of Newland et al11 where live and dead microfilariae was 13.6% while punctuate corneal opacities was 19.1%. Abiose12 reported that a single treatment with Ivermectin reduced the microfilaria in the cornea to 2% and 9% of pretreatment count after four months. In the surveyed communities two cases (0.2%) had dead microfilaria in the cornea. These communities had received one course of Ivermectin in the past three to six months prior to this study. The pre treatment microfilaria load was however, not established.

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Microfilaria in the anterior chamber: The prevalence of microfilaria in the anterior chamber was 4%. Fischer et al9 reported an average prevalence of 44% in Kabarole district of Uganda while Dadzie et al13 reported a reduction of 20%, four months after a single treatment with Ivermectin. Newland et al11 found microfilaria in the anterior chamber in 23.9% among 782 subjects in a survey of ocular onchocerciasis in a rain forest area of West Africa. The relatively low level of microfilaria in the anterior chamber of the eyes among the surveyed communities could have been because the communities had received Ivermectin in the previous three to six months prior to the study. However, there was no statistically significant relationship between the presence of microfilaria in the anterior chamber and the intake of Ivermectin. Cases have been observed in which microfilariae could be demonstrated in the eye over a period of time without any pathological changes resulting14.Iritis / iris atrophy: In this study the prevalence of both active and inactive iritis (anterior uveitis) of 3.4% was similar to that reported by Fischer et al9, 5.8%. Abiose12 reported that with the death of microfilaria, a torpid iritis/ uveitis develops. Uveitis is a non specific intra-ocular inflammation associated with ocular onchocerciasis due to toxins released by dead microfilaria or their motility. A more severe anterior uveitis may develop with the formation of inferior, posterior and peripheral anterior synerchiae which may be complicated by secondary cataract and glaucoma. The study findings are consistent with those of Fischer et al 9 and Abiose12. In Sudan keratitis, iritis, iridocyclitis synechiae and associated iris atrophy were reported14. The death of microfilaria provokes uveitis and repeated uveitis may result in complications such as iris atrophy, glaucoma, cataract, hypotony, chorioretinal degeneration and phthisis bulbi with resultant visual loss.Distribution of irreversible lesions: The prevalence of optic atrophy (6.4%) and sclerosing keratitis (5.2%) was highest in the age groups 45-54 years. The corneal opacities in sclerosing keratitis tend to be peripheral with a slightly clear central cornea hence lesser effects on the visual acuity. The findings in Pader showed cases with severe posterior segment pathology but little or absent anterior segment pathology.

A study by Newland et al11 in the rain forest area of West Africa revealed sclerosing keratitis prevalence of 5% among 800 respondents and was more common in older subjects. The prevalence of optic atrophy in hyperendemic rain forest varied from 1% - 4% in savanna communities of Cameroon to 6% - 9% in Guinea savanna of northern Nigeria15. Atrophy of choriocapillaries, choroido-retinal scaring and sub-retinal fibrosis and pigment disturbance at the disc margin with or without primary optic atrophy are advanced lesions which are sometimes seen. Berghout16 reported that patients with palpable nodules present with serious pathology of posterior segment

of the eye twice frequently as in non-onchocerciasis patients. A survey in Adjumani and Moyo districts (Uganda) by Ukety et al17 revealed that 2.8% of the respondents had irreversible eye lesions which included sclerosing keratitis, chorioretinitis and optic atrophy.

In Pader the most significant blinding lesion was optic atrophy which usually results from repeated optic neuritis. There was notably a higher affinity for the optic nerve than other ocular structures. The relationship between the presence of nodules and irreversible ocular lesions (x2 = 91.416, p-value 0.000), and the occurrence of irreversible lesions with positive skin snip (x2 = 400.982; df = 205, p-value 0.000) was statistically significant.

The development of ocular lesions correlates with the degree and duration of infection18. The pathogenesis of posterior segment pathology, which mainly includes optic atrophy and chorioretinital, degeneration has been attributed to a number of factors such as the role of microvascular occlusion of retinal vessels by dead microfilaria, effects of toxins released by the adult worms and dead MF, combined effects of toxins and avitaminosis A, genetic factors, toxic products of disintegrating microfilaria in the retina and choroid and the role of immune complexes11. Kirk 14 reported that hereditary factors, nutritional deficiencies and intercurrent infections have been regarded as contributory factors. Ogunrinade et al19 reported two strains of onchocerca volvulus in Nigeria; the blinding type which predominates the savannah biochime of West Africa and the non blinding found in the rain forest. Infestation by the former is associated with blinding ocular lesions which are rare in the latter. Studies have shown that the difference between blinding and non blinding onchocerciasis may be due to the differences in endemic parasite populations.

The high prevalence of optic atrophy in Pader district could be attributed to onchocerciasis. This is consistent with the findings of Abiose12 that there is a high prevalence of optic atrophy in onchocerciasis hyperendemic areas. In western and other parts of Uganda the onchocercaisis infestation is not blinding like in Northern Uganda and this has been attributed to the vector difference, Simulium Naevi. This study demonstrated co-relationship between visual impairment with the following variables: irreversible lesions, optic atrophy, nodules and positive skin snip hence suggesting that the onchocerca volvulus could be the responsible agent.Visual impairment: The study revealed that cataract was the leading cause of blindness in the surveyed community. Age related cataract globally accounts for 50% world blindness while the remaining 50% is distributed amongst the other diseases such as glaucomas 12.3%, age related macular degeneration 8.7%, corneal opacities (including trachoma) 8.7% and


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onchocerciasis 0.8%20. Pader district is hyperendemic for trachoma and hence the high prevalence of corneal scars and optic atrophy has been linked to onchocerciasis. The high number of blindness and severe visual impairment could be attributed to the sampling methodology.

CONCLUSIONS AND RECOMMENDATION

The results of this study indicate that the onchocerciasis in Pader district is a blinding type. Semi-annual Community Directed Treatment with Ivermectin (CDTI) by the Ministry of Health is recommended.

ACKNOWLEDGMENTS We extend our sincere appreciations to ENVISION/RTI Neglected Tropical Disease Control Programme for the financial support for the field investigations, the African Programme for Onchocerciasis Control and the WHO country office (Uganda) for supporting the REMO survey, Pader district leadership and the communities in the surveyed parishes. We are also indebted to the following team members whose extraordinary efforts made the study a success: E Tukesiga, B.V Abwang, S.W Oyet, J. Luciyamoi, P. Odonga and Buyinza. Further appreciation to the following institutions and Officers for releasing their staffs to participate in the survey: District Health Offices (Pader, Lamwo, Mbarara and Kabarole) and Gulu Regional Referral Hospital.

REFERENCES

1. WHO (1995). Onchocerciasis and its control. Report of a WHO Expert Committee on Onchocerciasis, Technical Report Series, No. 852, Geneva:WHO.

2. Ndyomugyenyi, R. The burden of onchocerciasis in Uganda. Ann. Trop. Med. Parasit. 1998; 92:S133-S137.

3. Watmon B (2007). Onchocerciasis in Aruu County Pader District; Report on Onchocerciasis seen during Eye Camps at Awere Health Centre III and Lacekocot Health Centre III, Pader District [Un-Published data].

4. Kish, L, Frankel, MR. Inference from complex samples. J Royal Statistical Society, Series B. 1974; 36: 1 37.

5. Bennet S, Words T, Liyange WM, Smith D. Simplified general methods for cluster sample surveys in developing countries. Quart. 1991; 44: 98-106.

6. Lakwo TL, Tukesiga E, Katongole C, Komakech JB, Oyet S, Odonga P. (2008). Report on the Rapid Epidemiological Mapping of Onchocerciasis in Kitgum and Pader districts, Northern Uganda. (Unpublished document).

7. Gilbert C, Foster A, Negrel AD, Thylefors B. Childhood blindness. A new form for recording causes of visual loss in children. Bull. WHO. 1993; 71 (5): 485-489.

8. Katabarwa M, Eyamba A, Habomugisha P, Lakwo TL, Ekobo S, et al. After a decade of annual mass ivermectin treatment in Cameroon and Uganda, Onchocerciasis transmission continues. Trop Med Intern Health; 2008; 13: 1196 -1203.

9. Fischer P, Kipp W, Bamuhiga J, Binta-Kahwa J, Kiefer A, Buttner DW. Parasitological and clinical characterization of S. Neavei transmitted onchocerciasis in western Uganda. Trop. Med. Parasit. 1993; 44: 311-321.

10. Krupp MA, Chatton MJ. Current medical diagnosis and treatment. Large Medical Publications. 1978; 94022: 892-893.

11. Newland HS, White AT, Greene BM, Murphy RP, Taylor HR. Ocular manifestations of onchocerciasis in a rain forest area of West Africa. Ophthalmol. 1991; 75(3): 163 - 169.

12. Abiose, A. Onchocercal eye disease and impact of Mectizan treatment. Annals Trop Med Parasitol. 1998; 92: S11-S22.

13. Dadzie KY, Remme J, Alley ES, De Sole G, Changes in ocular onchocerciasis four and twelve months after community-based treatment with ivermectin in a holoendemic onchocerciasis focus. Trans. Roy. Soc. Trop. Med. Hyg. 1990a; 84: 103-108.

14. Kirk R. Factors in the pathogenesis of ocular onchocerciasis. Bull. WHO. 1957; 16: 485-493.

15. Abiose A, Jones BR, Cousens SN, Murdoch I, Cassels-Brown A, et al. Reduction in the incidence of optic nerve disease with annual ivermectin to control onchocerciasis. Lancet. 1993; i: 130-134.

16. Berghout, E. Onchocerciasis and optic atrophy in the savannah area of Ghana. Trop Geog. Med. 1987; 39:323-329.

17. Ukety T, Nyathirombo A, Watmon B, Habomugisha P (2007). Evaluation of Onchocerciasis treatment in eight sentinel villages in Adjumani and Moyo districts, Uganda. (Unpublished document).

18. Fuglsang H, Anderson J. In: WHO (1987) Expert Committee on Onchocerciasis. World Health. Organisation. Technical Report series. 752, pp. 66.

19. Ogunrinade A, Boakye D, Merriweather A, TR. Unnasch. Distribution of blinding and non blinding onchocerca volvulus in Nigeria. http://www.jstor.org

20. Kocur Ivo. What is new at the back of the eye? Comm Eye Health. 2006; 19; (57); 1-3.

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