First Report of Presumed Parasitic Keratitis in Indians from the Brazilian Amazon

Cristina Garrido, M.D., and Mauro Campos, M.D.

Purpose. To describe corneal disorders in patients with systemic Cerqueira6 suggested that a hematophagous insect other than the parasitic disease. Methods. Cross-sectional study consisted of Culicoides was responsible for the transmission of M. ozzardi in ophthalmologic examinations, peripheral blood tests and skin bi- Brazil.7 Cerqueira6 defined the black fly Simulium amazonicum as opsies in 496 subjects (395 Indians and 101 non-indians) from the a possible vector at the village of Codajas on the lower portion of upper Negro River, Brazilian Amazon. Results. Mansonella oz- the Solimoes river in the Amazon region. This fly, in particular the zardi was detected in the blood of 140 (28.23%) subjects. Seventy- amazonicum group, can be the vector of both M. ozzardi and six (55.07%) of them also presented multiple nummular opaque superficial lesions in the cornea. None of the examined patients Onchocerca volvulus, in the Americas and Africa. In Africa and presented onchocercal-related skin lesions or positive skin biopsies Venezuela the black flies commonly bite the skin of the inferior for filaria. Conclusion. There was a significant association be- members but in Mexico and Guatemala the black flies usually bite tween mansonelliasis and keratitis. the upper body. The treatment of infected patients and the elimi- Key Words: Keratitis—Mansonella ozzardi—Amazon. nation of black flies8 are both methods of onchocerciasis and mansonelliasis prophylaxis. Most authors consider M. ozzardi to be a non-pathogenic para- site in humans. However, some researchers from the Amazon region define mansonelliasis to be an endoparasitosis that may cause Manson, in 1897, gave the name Filaria ozzardi to small, un- headaches, low grade fever, erythematous pruriginous papules, sheathed microfilariae with “sharp” tails, which were found in the painful joints, cold legs and inguinocrural adenitis.3,9,10 peripheral blood of aboriginal Indians living in the interior of Nigerian investigators studied blood and skin samples from 150 British Guiana. In 1929, Faust defined the genus Mansonella for F. patients with a clinical diagnosis of filariasis and ocular manifes- ozzardi, considering the morphological description on the micro- tations finding a prevalence of 16% for M. perstans and 4% for O. filaria and on the incomplete and sketchy descriptions of the volvulus; these results led the researchers to admit a possible as- adult’s worms provided by earlier workers.1 sociation between mansonelliasis and the ocular findings.11 Mansonella ozzardi, a New World filaria, is found in the Ca- Currently, there are no publications about Indians in the litera- ribbean and in Central and South America. In Brazil, endemic ture relating mansonelliasis and corneal disorders. This is the first areas are found in the state of the Amazon, nearby Solimoes, Purus paper describing nummular infiltrates in the cornea of Indian pa- and Negro Rivers, especially close to Indian population’s.2 tients living in an area of high M. ozzardi presence. Adults worms of M. ozzardi live in the mesentery and conjunc- tive subperitoneal tissue or alternatively, in the fatty tissue of viscera. The female worm is 6–8 cm long and the male is virtually unknown. Microfilariae circulate continuously in the blood. They PATIENTS AND METHODS are 200 ␮m long and 5 ␮m wide, unsheathed, with the somatic nuclei compacted together and the narrow caudal nuclei arranged This was a cross-sectional study carried out among 496 subjects, in a single rule that do not reach the thin extremity of the worm.3,4 of both sexes and various ages, living in Sao Gabriel da Cachoeira, The life cycle of the worm requires both man and insect hosts. a small town on the upper Negro River, in the Brazilian Amazon In the Amazon, the major vector is Simulium amazonicum (black (Fig. 1). The sample included 395 Indians (204 Aruaks, 132 Tu- fly). Development of the filaria in the insect is slow, occurring in kanos and 59 Makus) and 101 non-Indians. 9 days.5 An eye examination was performed in all individuals to detect Culicoides furens Mansonella ozzardi the presence of ocular lesions of onchocerciasis, one of the major The is also a vector of in 12 the Brazilian Amazon and in St. Vincent, Antilles.2 causes of blindness. The exam included visual acuity, biomi- croscopy, applanation tonometry and indirect ophthalmoscopy. After the eye examination, material for lab tests were collected: a) skin biopsies were obtained from the supra scapular and iliac-crest Submitted December 4, 1999. Revision received April 4, 2000. Ac- regions, using appropriate punches and skin snips (the samples cepted April 30, 2000. were preserved in both saline and buffered formaldehyde solu- From the Ophthalmology Department of Sao Paulo Federal University, tions); b) peripheral blood was obtained by collecting drops in Paulista School of Medicine, Sao Paulo, Brazil. Address correspondence to Dr. Mauro Campos, Department of Ophthal- three slides for smear preparations that were dehemoglobinized mology, Paulista School of Medicine, R Botucatu 820, CEP 04023/062, and stained with Giemsa. Data was analyzed using a Chi-square Sao Paulo, Brazil. test.

817 818 C. GARRIDO AND M. CAMPOS

TABLE 1. VA in both eyes after optical correction in individuals (Indians and non-Indians) with or without parasitic keratitis

Parasitic keratitis VA (OU) Presence, n (%) Absence, n (%) Total, n (%) 20/20 62 (81.58) 356 (84.76) 418 (84.27) Յ20/30 14 (18.42) 64 (15.24) 78 (15.73) Total 76 (100) 420 (100) 496 (100)

␹2 Calculated = 0.4920; ␹2 Crı´tic = 3.84. VA, visual acuity; OU, both eyes.

Indian population (Table 2). The prevalence of keratitis by age is presented in Table 3. One hundred and forty individuals had M. ozzardi in the peripheral blood; the highest prevalence was in the Indian group (Table 4). Mansonella ozzardi parasites were seen in the blood smears of patients with corneal lesions (Table 5). No filariae or microfilariae FIG. 1. Map showing the studied area and geographic distribution were found in skin biopsies. (from 1990) of M. ozzardi in Brazil.10 Other eye diseases diagnosed among the Indian population (395) included ametropia in 245 (62.5%) Indians, trachoma in 129 (32.6%), pterygium in 107 (27.1%), cataracts in 80 (20.2%), reti- RESULTS nal disorders in 28 (7.1%), glaucoma in 22 (5.6%), leukoma in 4 The corneal lesions found were characterized by non-confluent, (1.0%) and phitisis bulbi in 1 Indian (0.2%). Some patients pre- whitish nummular infiltrates, 2 mm or less in diameter, involving sented more than one ocular pathology. the anterior and mid stroma as small inflammatory foci. The over- laying epithelium was normal. The infiltrates, 2–8 lesions per eye, DISCUSSION were generally found in the periphery, surrounded by transparent cornea and with no signs of neovascularization or anterior chamber The occurrence of M. ozzardi has been described for more than reaction, as illustrated (Fig. 2). 40 years in the state of the Amazon, Brazil. It occurs in both Corneal lesions were equally detected in both sexes and they did Indians and in non-Indian populations. Attempts to control for this not appear to cause low visual acuity (Table 1) or photophobia. filariasis are infrequent because M. ozzardi is considered to be These lesions were more frequent in the Indian than in the non- non-pathogenic.1,13 This paper describes corneal lesions similar to those observed by other authors in onchocerciasis patients.14,15 In this series, however, there is no association with onchocercal skin lesions or O. volvulus microfilariae in skin biopsies. Ocular anterior segment disorders associated with onchocerciasis described in the literature include: conjunctivitis; nummular keratitis, similar to those observed in these series; linear keratitis, caused by the migration of the microfilariae through the corneal stroma; and sclerosant keratitis. The last represents a more severe condition associated to epithelial hyperplasia, an infiltration of

TABLE 2. Frequency of keratitis in Indians and non-Indians

Keratitis Indians, n (%) Non-Indians, n (%) Total, n (%) Presence 68 (17.22) 8 (7.92) 76 (15.32) Absence 327 (82.78) 93 (92.08) 420 (84.68) Total 395 (100) 101 (100) 496 (100) FIG. 2. Slit lamp photography of a patient revealing two distinct sites of corneal lesions in the peripheral cornea. The adjacent tissues ␹2 Calculated = 4.66; ␹2 Critic = 3.84. appear normal. n, number of patients.

TABLE 3. Prevalence of keratitis by age in Indians and non-Indians

Indians Non-Indians Total Keratitis Յ18 years >18 years Յ18 years >18 years Յ18 years >18 years Presence (%) 2 (4.65) 66 (18.75) 0 (0.00) 8 (9.64) 2 (3.28) 74 (17.01) Absence (%) 41 (95.35) 286 (81.25) 18 (100.00) 75 (90.36) 59 (96.72) 361 (82.99) Total (%) 43 (100.00) 352 (100.00) 18 (100.00) 83 (100.00) 61 (100.00) 435 (100.00)

Cornea, Vol. 19, No. 6, 2000 PARASITIC KERATITIS 819

TABLE 4. Results of blood tests in Indians and non-Indians to a low prevalence of mansonelliasis in children and young adults.19 M. ozzardi (blood) Indians, n (%) Non-Indians, n (%) Total, n (%) Although most of the lesions in this series were peripheral and did not lower visual acuity, the findings in this study suggest the Positive 128 (32.41) 12 (11.88) 140 (28.23) Negative 267 (67.59) 89 (88.12) 356 (71.77) possibility that M. ozzardi can be pathogenic. Total 395 (100.00) 101 (100.00) 496 (100.00) REFERENCES ␹2 Calculated = 15.73; ␹2 Critic = 3.84. 1. Oriel TC, Eberhard, ML. Mansonella ozzardi: a redescription with comments on its taxonomic relationships. Am J Med Hyg 1992;31: Bowman’s and corneal neovascularization. Intraocular signs in- 1142–7. clude uveitis and retinal disorders.16,17 2. Rey L. Parasitologia. In: Rey L, ed. Onchocerca volvulus: oncocercose A study conducted in Pauinı´, a small town on the Purus River, e outras filarıáses, 2nd edition. Rio de Janeiro: Guanabara Koogan, revealed 20 non-Indian habitants with peripheral corneal opacities 1991:553–64. 3. Pessoâ SB, Martins AV. Famı´lias Filariidae e Dracunculidae.In: among 524 patients examined; 4 were submitted to skin biopsies Pessoâ SB, Martins AV, eds. Parasitologia me´dica, 11th ed. Rio de and blood-tests. No filariae were seen in the skin snips and two of Janeiro: Guanabara Koogan, 1998:610–8. the blood smears contained Mansonella sp. The authors suggested 4. Nutman TB. Experimental infections of humans with filariae. Rev a presumed association between the corneal lesions and manson- Infect Dis 1997;13:1018–22. elliasis.16 5. Shelley AJ, Luna Dias APA, Maia-Herzog M, et al. Identification of vector species (Diptera Simuliidae) of human onchocerciasis in the In the present series, there was a positive association between Amazonia focus of Brazil and Venezuela. 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Correlation between the presence of keratitis and M. habitantes do municı´pio de Pauinı´ e possı´vel associaçao entre lesoes Arq Bras Oftal ozzardi in peripheral blood corneanas e mansonelose na Amazoˆnia. 1998;61:674– 82. Keratitis 17. Diallo, JS. Impasses parasitaires et larva migrans exotigues. In: Diallo M. ozzardi JS, ed. Manifestations ophthalmologiques des parasitoses. Paris, Mas- (blood) Presence, n (%) Absence, n (%) Total, n (%) son, 1985:309–20. Positive 76 (100.00) 64 (15.24) 140 (28.23) 18. Ewert A, Smith JH, Corredor A. Microfilariae of M. ozzardi in human Negative 0 (0.00) 356 (84.76) 356 (71.77) skin biopses. Am J Trop Hyg 1981;30:988–91. Total 76 (100.00) 420 (100.00) 496 (100.00) 19. Nathan MB, Beckles G, Tikasingh ES, et al. Parasitological and clinical studies of W. Bancroft and M. ozzardi in coastal North Trindad, ␹2 calc = 224.06; ␹2 crit = 3.84. West Indies. WIMedJ1982;31:168–76.

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