Ocular onchocerciasis: risk factors for blindness

i.. , .. ;.d-r- r$_ v. WORLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTE 0NcH0/wP/ 75. 16 ORIGINAL: ENGLISH EXPERT COMMITTEE ON EPIDEMIOIOGY OF ONCHOCERCIASIS Geneva 1O-18 Noverober 1975 DrafE agenda item 5.3 OCUIAR ONCITOCERCIASIS: RISK FACTORS FOR BLINDNESS by J. Andersorrl a.rd H. Fuglsangl To the au I knowledge only two ophthalnologists, Budden (L957) and Rolland (L974), development of ocular onchocerciasls in African coununities. The present wor will be based partly on their experiences, but mainly on the preliminary results of a four-year follow-up of 15 out of 16 groups of villages from the rain-forest and Sudan-savanna zones of Cameroon. 1. COMM'NITY RISK FACTORS Duke (1968) defined the annual transmission po tenEial as the number of Onchocerca volvulus infective larvae wtrich could be inoculated into a rnan during one year if all the infective flles bltlng hin were to transmit their full load of larvae. Duke et aI. (L972, L975) also showed that this annual transmission potential was associated with the pattern of onchocerciasis, in both rain-forest and Sudan-savanna in Cameroon. In the latter area in particular, a high transmission potential was associated r^rith a high prevalence of blindness due to onchocerciasis. On Ehe banks of the Sinulium damnosum breeding rivers the annual transmission potential could rise above a cerEain rrcriticalrr level, which was incompatible with village survival. In the rain-forest, onchocerciasls never led to very high blindness rates, even when the annual transmi.ssion potential was as high as 90 OOO. This would appear to support the view that it is not the absolute degree of transmission, but rather the sErain of parasite which determines the severity of the disease as a cause of blindness in the Sudan-savanna zone (Duke et aI., L966; Lewis & Duke, 1966; Duke & Anderson, 1972; Garner et al. , L974). It was also shoqm that, in savanna villages at distances varying from 2 to 20 krn from the nearest perennial S. damnosum breeding site, the prevalence of infection with 0. volvulus was almost the same. However, the intensity of infection, as measured by the number of microfilariae per mg of skin and the number of microfilariae in the cornea and anterior chamber, was correlated with Ehe annual transmission potential. It is thus the intensity rather than the prevalence of infectlon which determines the severity of ocular onchocerciasis in a conurunity. Knowledge about nutri-tional and irmunopathological risk factors is insufficient, with respect both to the paraslte and the host. These factors may explain the higher prevalence of blindness in the savanna compared with the rain-forest. It has also been found that 1 Medical Research Council grantholders, London, England. N ,.4 -) UJ The issue of this document does not constitute formal publication. lt should not be reviewed, abstracted or quoted without the agreement of the World Health Organization. Authors alone are responsible for views expressed in signed articles. Ce document ne constitue pas une publication. ll ne doit faire I'objet d'aucun compte rendu ou r6sum€ ni d'aucune citation sans l'autorisation de I'Organisatron Mondiale de la Sante. Les opinions exprimdes dans les articles sign6s n'engagent que leurs auteurs. 0NcH0/wP/ 7s. 16 Page 2 corneal droplet (spheroidal) degeneration was almost confined to the savanna ln Cameroon (Anderson & Fuglsang, in prep.). The cause of this condition is not known, but its distribution elsewhere suggests that it is due to climatic factors such as exPosure to high levels of ultraviolet 1ight, or desiccation (Freedman, L973). 2. ]NDIVIDUAL RISK FACTORS Many patients who came with severe ocular onchocerciasis to a temPorary eye clinic in the Sudan-savanna of north Cameroon gave a history of camping for some months close to a river, for either farming, fishing, or hunting purposes. In southern Sudan we were taken to a river ferry along side an S. darnnosum breeding site at a partially broken down causeway. Three of the ferrymen were completely blind from onchocerciasis, and the fourth was partially blind. The local ophthalmologist had rightly labelled their disability occupational, and asked for proper compensation. It is well known that more males than females develop severe ocular onchocerciasis, but the reasons for this are still unknown. It could be that riloEen are less exposed to infectlve bites of S. damnosum , or that some hormonal factors are rrprotectivert agai.nst the develoPment or pathogenicity of the parasite in the feoale. Ash & Riley (1970) found that rnale Meriones unguiculaEus $rere much more susc eptible to infecrion wiEh Brugia spp. than were fernales. This suscepEibility was due, at least in part, to the action of testosterone(wesley & Ash, L972). Sucharit & Macdonald (1972) found that young male rats were more susceptible to infecEion than vrere mature male rats. Denham (L974), injecting B, pghangi larvae into sexually inrnature cats, found virtually no difference between the sexes in Ehe percentage of animals becoming patent, nor in the pre-patent periods, though females seemed to have lower microfilarial levels than males. Anderson et aL. (L974) found the same prevalence of positive skin snips in males and femeles over the age of five years, buE. while the fernales showed a gradual increase in skin density with age, the 15-19 year old males in both rain-forest and savanna had already reached peak levels. Dr S. Welch, Department of Biochernistry, The London Hospital Medical School, analysed blood groups from patients with lesions of the posterior segment of the eye due to onchocerci-asis (Bird et al. , L975), and found an abnormal distribut.ion of the MN groups. This may suggest that some patients with a special genetic pattern are more 1ikely to develop eye lesions than others. More studies are required along these lines, since they may be of importanee in the prevention of blindness. 3. RISK SIG\IS AND SYMPTOMS For the pioneers of onchocerciasis in Guaternala, the correlation between eye lesions and head nodules was so obvious that a nodulectomy campaign involving removal of all head nodules was already underway in 1933. In a report to the World l{ea1th Organization, Duke & Lartigue(1966) sEated that I'there can be little doubt that, by lowering microfilarial concenEraEions in the head region, the campaign has greatly reduced the incidence of severe eye lesions and blindnessrr. Figueroa-Marroquin (L974) also claimed that blindness had decreased in Guatemala as a result of nodulectomy campaigns. In Africa, relatively little attention has been paid to the head nodule in respect to ocular lesions. Rodger (1958) stressed its importance as a danger to the eye, and pointed out (1957) the difficulties in head nodule detection. Lagraulet (L972) stated that there was a direct relationship between the intensity of infection with O. volvulus and the severi ty of ocular lesions, but that these were unrelated to nodule locat ion. It was mainly the very high frequency of head nodules in children and young adults who had come spontaneously with severe eye lesions that called the authorsr attenEion Eo the danger of the presence of an adult worm close to the eye. Palpable head nodules were found in about one in four of 483 patients who came in this way to a temporary eye clinic in the Cameroon savanna. They were also present in about one in three of 14O patients with lesions oNcHo/wP/75.16 Page 3 of the Posterior segment of the eye lcho were assembled in the same area for a special sEudy(gira et al. , L975), as well as in a similar proportion of rain-forest cases of posterior segment lesion. In our first population study (Anderson et al. , Lg74), nodules were found on Ehe head and/or neck in only 1.4% Ln the rain-forest and O .5% Ln the savanna. In ourfollow-up, the corresponding flgures were 5.8% and 5.17., and major eye lesions lrere present inthe najority of cases with a head nodule. Thls was particularly marked in the savanna nales over the age of 15 (Fuglsang & Anderson, in prep.). There is no doubt, however, that many head nodules were missed, particularly in the first survey, and probably rnainly anong adults, whose hair styles often made proper palpation inpossible. In agreement with Rodger ( Lg57), head nodules, at any rate those containing live worms, were usually smalI, flat, and hard, andtightly adherent to the underlying peri-osteum. They were therefore often hardly visible, even on a shaved head, and the patient hiaself would frequently have to locate his nodule forthe examiner. They could be found anywhere on the head, but were particularly difficult todetect when deeply situated behind or in front of the ear, or deep to the mestoid process.In some caaes, Post-auricular or occipital lynph nodes were confused with onchocercomrta. rn cases wlth high microfilarial densities on the head, these nodes were often swollen and contained microfilariae (Connor, personal conrrunication), but usually they were softer than onchocercomata. In vi.ew of the above difflculties, any standardized examination for head nodules should probably include a direct question to the patient about their presence. There is some evidence that a nodule close to the eye is of partlcular danger Eo thePosterior seFent of the eye (Fuglsang & Anderson, in prep.), since the proportion of patientswith optic nerve disease and choroidoretinitis vrErs particularly high among those withpalpable head nodules. rn the cases studied by Bird er aI. (igzsl, ir is likely that a freelying Lorm or inpalpable nodule ltas present close to the eye in moat cases, Bi-nce the vastmajority showed very high concentrations of microfilariae in the skin at the outer canthus.This raises the question of whether eye lesions Eay often precede Ehe foroation of thepalpable nodule, and also of whether it is of curative or therapeutic value to reoove thenodule. Although there is no doubt in the authorsr minds about the danger to the eye of anadult worltr on the head in African onchocerciasis, it is realized that further studles arenecessary Eo find out if iEs early reooval can halt the development of eye lesions. Muchdanage uray have been done by the tioe the nodule is forued, and a method of detecting freelylng !'orms would be highly desirable. However, very simple health education could createawareness of this probleo in onchocerciasis areaa. rt is admitted that sooe children with easily detectable nodulee on the head show nosign of eye involvement. Ho!f,ever, their parents often reveal that they have pierced thenodule at some stage' thus killing the enclosed worm. Lagraulet (Lg72) stated that abour8o7' of the nodules in children under 10 years of age showed a degenerative processl betweenthe ages of 20 and 4o about half the nodules ,.." "til1 active, ih".""" 1n patients over45 years of age, less than @7. contained live hronnn. This night suggest that, children arelrmunologlcallyrpre competent than adulrs, or rhat rhey are born with;;.;-;;"i;i""...r- Anderson et al. (1975) de@onstrated that the presence of a palpable head nodule rrasassociated with a high concentrati.on of microfilariae in the skin at the outer canthus, andthat this in turn loas associated with a large number of microfilariae in the cornea andanterior chamber of the eye. Both Budden (1957) and Rolland (Lg74) point to the presence ofmicrofllariae in the anterior chamber as a risk eign. However, the number of microfilariaeseen in the anterlor chaober at any one examinatlon shows considerable variation (Anderson& Fuglsang, 1973), and furthermore the examination requi.res special equipment and speciallytrained personnel. rt is a question whether the most objective earry warning of danger tothe eye is not the detecti-on of microfilariae at the outer canthus. This examination couldeasily be perforrned by paramedical personnel. Anderson et al. (1975) gave therrcritical, 1 nodule The youngest nodule carrier observed by us in carneroon lrasr aged about 15 nonEhs.contained a single non-gravid fan:fs O. volvulus (Connor, personal comunicatlon). the oNcrro/wP/75.16 Page 4 leveI as 10 microfilariae per mg, but further studies may show that five microfilariae per mg also Present. risks to the eye. Further studies are also required to evaluate the prognostic value of the presence of nicrofilariae in the blood and urine with respect to ocular onchocerciasis. Fuglsang & Anderson (1974) found nicrofilariae in a single 2 ro1 venous blood sample in 59 of 66 patients (89.4%) with ocular onchocerciasis, and in 1O m1 urine samples Ln 63.6%. There is general agreenent that night blindness and a reduced visual field are warning symptoms and signs of importance (Toulant & Boithias, 1954; Budden, 1958; DrHaussy eE al., 1963; Qu6r6 et al., 1965; Vedy et al., L97L; Bird et aL., L975). The cenrral vision ofren ra'mains normal for a long time, and a test of central visual acuity alone is thus of limited value in the early detection of potenEial candidates for blindness in onchocerciasis areas. It is possible to perform a simple confrontation test in the field in order to detect visual field defects, but an equally simple tesE for dark adaptation is desirable. However, the patient himself or his relatives are often a\rare of field defects and poor night vision, and a direct quesEion to that effect should perhaps be part of any standardized examination. Finally, it must be pointed out that it is unknown whether night blindness and reduced visual fields are early or late warning s)imptoms. It may well be that irreparable darnage has been done before they appear. Watering and photophobia are often present with massive microfilarial invasi-on of the anterior segment of the eye, and, in contrast to the above, they frequently pronpt the patient Eo seek help, if such is available. 4. SUMMARY Based on the literature and our ovm experience, it ls pointed out that the risk of going blind from onchocerciasis is higher in the savanna than in the rain-forest in Africa. In both areas the risk increases with the intensity of infection, as measured by the number of detectable microfilariae in the skin and eye. There ls strong evidence that the differences between rain-forest and savanna are due nainly to different strains of the parasite. However, our knowledge is insufficient concerning climatic factors, and concerning nutritional and imunopathological factors in both the host and the parasite. Certain people (e.g. farmers, hunters, fishermen, ferrynen) who work close to S. daonosum breeding sites are particularly exposed to the risk of blindness. However, further studies are necessary to find out why more mr les than fema les go blind, and to assess the possible importance and prognostic value of genetic markers Possible warning spptoxns and signs include: the presence of a head nodule; a high concentration of mf/m8 of skin close to the eye; m2ny microfilariae in the cornea and/or anteri.or chamber; many microfilariae in the blood and urinel (v) night blindness; (vi) reduced visual fields. Further studies are required to evaluate their relative significance and application in the field. (i) ( ii) ( iii; (iv) a0Ncn0/lrP/ 7s. 16 Page 5 REFERENCES Anderson, J. & Fuglsang, II. (1973) Variation in numbers of microfilariae of Onchocerca volvulusin the anterior chamber of the human eye, Trans. roy. Soc. trop. Med. Hyg. , 67, 544-548 Anderson, J. & Fuglsang, H. (in preparation) The prevalence of corneal droplet degeneration in a coumunity in the Sudan-savanna of Cameroon Anderson, J., Fuglsang, I{., Hamilton, P. J. S. & l.Iarshall, T. F. de C. (L974) Studies on onchocerciasis ln the United Cameroon Republic. II. Comparison of onchocerci.asis in rain-forest and Sudan-savanna, Trans. roy. Soc. trop. Med. Hyg. , g, 209-222 Anderson, J., Fuglsang, Il., Hanilton, P. J. S. & l,Iarshall, T. F. de C. (1975) The prognostic value of head nodules and microfilariae in the skin in relatlon to ocular onchocerciasis, 2., Tropenmed. Paraeit . , 26, 191-195 Ash, L. R. & Riley, J. M. (1970) J. parasir,., 56,962-9681. 969-973 Bird, A. C., Anderson, J. & Fuglsang, Il. (1975) The morphology of posterior segment lesions of the eye in patients with onchocerciasis, Brit. J. Ophthal. , 1n Press Budden, F. H. (1957) Natural history of onchocerciasis, Brit. J. ophthal ., !, 2L4-227 Budden, F. H. (1958) The aeriology of Trans. roy Soc. trop. Med. Itye the ocular lesions assoclated with onchocerciasis, ' !, 5OO-5O8 Denham, D. A. (L974) Studles with Brugia pahangi. 6. The susceptibility of rnale and femafs cats to infection, J. Parasit. , @, 642 Drllaussy, R., Boyer, R. & Aubert, L. d6g6n6rescence tap6to-16tlnienn 1185-1211 (1963) Les fonctions visuelles dans 1a pseudo- e drorigine onchocerq ulenne, Ann. Oculist. Paris , 129, Duke, B. o. L. (1968) Studies on factors influencing the transmission of onchocerclasi.s.IV. The biting cycles, lnfecElve biting density and Eransmission potential of rforestr S. dnmnogum Ann Med. Parasit. , P!, 95-Lo6 Duke, B. O. L. & Lartigue, J.-J. (1966) Cheootherapy and other clinical methods used in theindividual treatoent of onchocerciasis and in rnass campaigns (Unpublished document wHo/oNclro/66. 46, pp. 1-38) Duke, B. O. L. &Anderson, J. (L972) A comparison of lesions produced in the cornea of the rabbit eye by ulcrofilariae of the foreet and Sudan-savanna strains of onchocerca volvulus from Cameroon. I. The cllnical picture, Z. Tropenmed. parasit.,4r 354-368 Duke, B. 0. L., Lewis, D. J. & Moore, p. J. (1966) Onchoc erca-!_ir"ti* comp lexes . Transmissi.on of forest and Sudan-savanna s trains of Onchoc erca volvulus, fromI from various West African bioclioatic zonea, Ann. trop Duke, B. O. L., Moore, P. J. &Anderson, J. (L972) Studies on factors influencing the transuission of onchocerciasis. VII. A comparison of the onchocerca volvulus transnissi.on potentials of Simulium damnoeuo populations in four Caneroon rain-forest vi 1lages and the pattern of onchocerclasls aseociated therewith, Cameroon, by Med. Parasit. Simulir:o daonoglr , 60, 318-336 I 66, 2L9-234 Ann. Med. Parasit. oNcHo/wP/75.16 Page 6 Duke, B. O. L., Anderson, J. & Fuglsang, H. ( 1975) The Onchocerca volvulus transmission potentials and associated patterns of onchocerciasi.s at four Cameroon Sudan-savanna villages, @., 26, L43-L54 Figueroa-Irtrarroquin, H. (1974) In: Regearch and control of onchocerciasis in the rdestern hemispherer , P. 10O Freedman, A. (1973) Climatic droplet keratopathy. I. Clinical aspects, Arch.Ophthal.,92, L93-L97 Fuglsang, H. & Anderson, J. (L974) Mlcrofilariae of Onchocerca volvulus in blood and uri-ne before, during, and after treatment with diethylcarbamnziner J. Helainth. , 48, 93-97 Fuglsang, H. & Anderson, J. (in preparation) The head nodule and ocular onchocerciasis Garner, A., Duke, B. O. L. & Anderson, J. (L974) A comparison of the lesions produced in the cornea of the rabbit eye by microfilariae of the foreet and Sudan-savanna strains of Onchocerca volvulus from Cameroon II. The pathology, Z. Tropenmed. Parasit., 24, 385-396 Lagraulet, J. (L972) Epideniology of ocular onchocerciasis in French-speaking countrles of West Africa, IE:j:_Eg9:_99i., !, 1153-1155 Lewis, D. J. & Duke, B. O. L. (1966) Onchocerca-Simulium complexes II. Variation in West African Simulium daronosum Ann. trop. Med. Parasit , 60, 337-346 Qu6r6, M.-A., Larivitsre, M. & Razafinjato, R. (1965) Les compllcations oculaires de a lronchocercose: probldme du prognostic visuel chez les suj Afr. noire Langue frane., 10, L9-2L ets traites, Bull. Soc. m6d Rodger, F. C 49s-508 (1957) New observatlons on ocular onchocerciasis, Bull. Wld lllth Or 16 Rodger, F. C. (1958) Comparison of the effect upon onchocerciasis of five drugs and selection of the one best able to prevent ocular comp 52, 462-467 lications, Trans. roy. Soc. trop. Med. tlyg., Rolland, A. (L974) R6sultats de deux examens oculaires pratiques i six ans drintervalle, dans deux villages onchocerquiens de Haute-Volta (Unpublished document. !HO/ONCIIO/74.L12) Sucharit, G. & Macdonald, W. W. (L972) Erygfe peha!€l in sna1l laboratory anioals: the screening of infection rate, S.E. Asian J. trop. Med. Publ lllth , 2, 347-354 Toulant, P.-F. & Boithias, R. trop., L4, L9L-L99 (1954) Les 16sions oculaires de ltonchocercose africaine, Med. Vedy, J., Sirol, J. & Coulm, J. (1971) Ia r6tinopathie ponctuEe albescente onchocerquienne, 479-486Bu11. Soc. Path. exot 64 Wesl-ey, I. V. & Ash, L. R. (L972) Paper presented at a meeting of the American Society of Parasitologists , 1972 * * *