2 Parasitic Diseases

55 ACANTHAMEBIASIS 136.9

(Acanthamoeba Keratitis)

John Everett Sutphin, MD

Kansas City, Kansas

ETIOLOGY/INCIDENCE

Four genera of the free-living amoebae are known to cause human disease: Acanthamoba spp., Balamuthia mandrillaris, Naegleria fowleri and Sappinia diploidea. Naegleria spp. were first associated with fatal meningoencephalitis in 1965. Most subsequent rapidly fatal cases have been associated with Naegleria fowleri, which enters through the mucous membranes and causes death within 5 to 7 days.

The more chronic form of granulomatous encephalitis has been attributed to several species of Acanthamoeba. In 1973, the first case of iridocyclitis attributed to Acanthamoeba was described, and in 1974, Acanthamoeba keratitis was recognized. Acanthamoeba spp. have been implicated in other infections, including disseminated granuloma of the skin, pneumonitis, external otitis and osteomyelitis. Keratitis is reported with eight species of Acanthamoeba (A. castellani, A. polyphaga, A. hatchetti, A. culbertsoni, A. lugdunensis, A. quina, A. rhysodes and A. griffini). All are in the cyst morphologic Group II except A. culbertsoni in Group III. These species are found predominantly in genotype group T4, but also in T3, T6, and T11.

Acanthamoeba keratitis (Figure 55.1a,b) has been reported from North and South America, Europe, Asia, Africa and Australia. The genus Acanthamoeba is found ubiquitously in nature, commonly in fresh water and soil, but it has also been isolated from dust, hot tubs, air filters, cooling towers, sewage, salt water and, most ominously, contact lens cases. The annual instance among contact lens wearers may be as high as 1 in 30,000.

The organism exists in the free-living form (trophozoite) and in the encysted form. Encystation is induced by changes in the environmental osmolarity or other noxious stimuli. Cysts are highly resistant to freezing, desiccation, and disinfection, including standard chlorination of the water supply.

Acanthamoeba organisms can be found as part of the normal flora of the human mouth and pharynx, and serologic evidence of immunity is present in over 80% of the population. The peak of the epidemic of keratitis in the United States was in the mid-1980s, but the infection continues to occur at a steady or an increasing rate despite improved methods of disinfection and recognition of the risk factor of the use of tap water or

nonsterile saline in caring for contact lenses. Acanthamoeba spp. may harbor waterborne bacterial endosymbiants such as

Legionella pneumophila and Mycobacterium avium among others.

COURSE/PROGNOSIS

Clinical keratitis can range from very mild, which may mimic epidemic keratoconjunctivitis or have the distinctive sign of perineuritis, to severe, with ring infiltration, descemetocele formation and perforation. The keratitis is commonly confused in its early phases with herpes simplex keratitis and may even coexist with herpes simplex. The clinician must maintain a high index of suspicion for this condition.

Keratitis typically follows exposure of an epithelially compromised cornea to a contaminated water source. Epithelial compromise includes any form of contact lens wear (daily disposable soft lenses, extended-wear soft lenses, gas-permeable, or hard polymethylmethacrylate), epithelial disease such as dry eye, herpes simplex keratitis and ocular injuries, such as abrasions or foreign bodies. Exposure to a contaminated water source can result from contact lens cases or solutions, municipal water supply, brackish water, pond or lake water, hot-tub water, or water that has been contaminated by animals. Trophozoites feed on gram-negative bacteria and cyanobacteria. Organisms prefer an environment of 25º to 35ºC. The most common species are A. culbertsoni, A. polyphaga, and A. castellani.

DIAGNOSIS

Early infection begins as epitheliopathy, which progresses to subepithelial changes, followed by inflammation along the nerves; finally, as the organism progresses deeper, a double ring is seen.

●Initial stage: redness, irritation, foreign body sensation, photophobia, localized punctate staining or microcysts, pseudodendrite or corneal epithelial lines, radial perineuritis, limbitis, and mild iritis.

●Transient stage: stromal infiltrates progress to form a ring or double ring (almost pathognomonic).

●Final stage: corneal abscess, central stromal edema similar to disciform keratitis, delayed-onset subepithelial infiltrates, neurotrophic keratitis, descemetocele, severe iritis and hypopyon.

There is severe pain in any of the three stages. Steroid therapy delays diagnosis, and prognosis worsens with diagnosis that

2 SECTIONDiseases Parasitic •

a

c

FIGURE 55.1. a) Clinical picture of advanced acanthamoeba keratitis ring infiltrate. b) Clinical picture of early acanthamoeba keratitis with perineuritis. c) Confocal microscopy showing double walled cysts of acanthamoeba. d) Histopathology of corneal button showing cysts and trophozoites in the deep cornea. (H and E)

occurs more than 4 weeks from the onset. Clinicians must have a high index of suspicion, particularly when a patient with keratitis fails to respond to the usual antibacterial, antiviral, or antifungal therapies. In a contact lens wearer with severe pain, the diagnosis must be considered early.

Laboratory findings

●Corneal scrapings under bright-field or phase-contrast microscopy or stained with hematoxylin and eosin, Gram’s, Giemsa, or cellufluor white.

●Typical polygonal, double-walled cysts.

●Trophozoites show spiky appearance on electron microscopy or sharp borders with prominent karyosome and foamy cytoplasm under light microscopy.

100

b

d

●Cultures plated on blood agar, chocolate agar, or nonnutrient agar overlaid with killed Escherichia coli or Klebsiella spp.

●Observe plates with microscope for typical tracks of the trophozoite.

●Immunofluorescent staining of cultured amoeba or original scraping.

●Polymerase chain reaction (PCR) of amoebic RNA or DNA (mitochondrial or genomic).

●Confocal microscopy (Figure 55.1c); recognition of refractile spots of appropriate size (20 to 40 μm) representing trophozoites and cysts in the epithelium and anterior stroma.

●Advanced cases, corneal biopsy or therapeutic keratoplasty specimen for histopathology or culture (Figure 55.1d).

Acanthamebiasis • 55 CHAPTER

2 SECTIONDiseases Parasitic •

DIAGNOSIS

Clinical signs and symptoms

●Retina: retinal or subretinal tracks with or without motile worm, recurrent evanescent gray-white lesions of retinitis, absent or a few small hemorrhages, focal or diffuse hypopigmented tracks in the pigment layer, pigment migration, sheathed or narrowed vessels or both, subretinal mass (granuloma).

●Choroid: sometimes small infiltrates or scars.

●Optic disk: edema, pallor.

●Vitreous: vitreitis.

●Ciliary body: snowbanking in pars plana.

●Iris: iritis.

●Transient unilateral blackouts in vision lasting a few seconds may indicate optic disk edema.

Laboratory findings

The motile nematode in the retina is diagnostic of DUSN or OLM. The subretinal tracks, created by the larger-nematode larva such as B. procyonis, are commonly visible nearby. The Goldmann fundus contact lens or the 78D or 90D funduscopic lenses are useful to find the motile larva.

●Serum can be examined for antibodies to B. procyonis by indirect immunofluorescence and T. canis by enzymelinked immunosorbent assay (ELISA) and Western blot analysis. Toxocara ELISA is available from the Centers for Disease Control and Prevention (Atlanta, GA).

●Unless peripheral eosinophilia or neurologic disease (neural larva migrans) is present, no further investigation is necessary.

Differential diagnosis

●Pigment mottling in the retina caused by the tracks of a motile worm (pseudoretinitis pigmentosa) resembles retinitis pigmentosa.

PROPHYLAXIS

●Risk of transmission of B. procyonis to humans exists through ingestion of eggs from feces of raccoons. These eggs remain viable and infective in the soil for months to years.

●Risk of transmission is increased because raccoons commonly live in residential and recreational areas.

●Children are especially at risk through accidental hand-to- mouth transfer of infective B. procyonis eggs.

●Raccoons defecate on downed logs, on hearths or decks of homes and in barns.

●Places where raccoons have nested or have been caged should be avoided.

●Handwashing should be done immediately after contact with soil or waste material contaminated by raccoons.

TREATMENT

Systemic

●The anthelmintic oral agent, thiabendazole, appears to have varying success for small-nematode larva such as T. canis in DUSN.

FIGURE 56.1. A 2000 micron long motile larva (arrowhead) is superotemporal to the right macula, with hypopigmented subretinal tracks (arrows) in a 13-year-old girl, who had a pet raccoon. Prompt photocoagulation destroyed the larva.

Laser surgery

●Prompt laser photocoagulation of the motile worm in the retina is preferred as the most effective treatment of DUSN. The fovea is avoided during laser treatment (Figure 56.1).

Surgery

●Difficulty in identifying the worm has been reported with surgical excision of the motile nematode larva.

REFERENCES

Fox AS, Kazacos KR, Gould NS, et al: Fatal eosinophilic meningoencephalitis and visceral larva migrans caused by the raccoon ascarid, Baylisascaris procyonis. N Engl J Med 312:1619–1623, 1985.

Gass JDM, Callanan DG, Bowman CB: Oral therapy in diffuse unilateral subacute neuroretinitis. Arch Ophthalmol 110:675–680, 1992.

Gass JDM, Gilbert WR, Jr, Guerry RK, Scelfo R: Diffuse unilateral subacute neuroretinitis. Ophthalmology 85:521–545, 1977.

Goldberg MA, Kazacos KR, Boyce WM, Ai E, Katz B: Diffuse unilateral subacute neuroretinitis: morphometric, serologic, and epidemiologic support for Baylisascaris as a causative agent. Ophthalmology 100:1695– 1701, 1993.

Huff DS, Neafie RC, Binder MJ, et al: The first fatal Baylisascaris infection in humans: an infant with eosinophilic meningoencephalitis. Pediatr Pathol 2:345–352, 1984.

Kazacos KR, Raymond LA, Kazacos EA, Vestre WA: The raccoon ascarid: a probable cause of human ocular larva migrans. Ophthalmology 92:1735–1744, 1985.

Kazacos KR, Vestre WA, Kazacos EA, Raymond LA: Diffuse unilateral subacute neuroretinitis syndrome: probable cause. Arch Ophthalmol 102:967–968, 1984.

Mets MB, Noble AG, Basti S, et al: Eye findings of diffuse unilateral subacute neuroretinitis and multiple choroidal infiltrates associated with neural larva migrans due to Baylisascaris procyonis. Am J Ophthalmol 135:888–890, 2003.

Pork SY, Glaser C, Murray WJ, et al: Raccoon roundworm (Baylisascaris procyonis) encephalitis: case report and field investigation. Pediatrics 106:56–60, 2000.

Raymond LA, Gutierrez Y, Strong LE, et al: Living retinal nematode (filar- ial-like) destroyed with photocoagulation. Ophthalmology 85:944–949, 1978.

Baylisascaris • 56 CHAPTER

2 SECTIONDiseases Parasitic •

sis is the infestation of humans by Cysticercus cellulosae, the larval form of Taenia solium or the pork tapeworm. It is the most common ocular tapeworm infestation occurring in endemic regions such as Africa, South-East Asia (Indian subcontinent), Mexico, South America and Eastern Europe. Cysticercosis continues to be a public health problem even in the developed nations due to easy air travel.

Man is the definitive host. The adult worm, consisting of a head or scolex with its double row of hooks and four suckers, neck and segments or proglottids, inhabits the human small intestine. The terminal gravid segments are passed into the feces and eaten by pig, the usual intermediate host. On reaching its alimentary canal, these hatch, penetrate the gut wall to gain entrance into the systemic circulation and the naked oncospheres are ultimately filtered out into the striated muscles and various tissues, where they undergo development, encyst and expand into fluid-filled bladders to form cysticerci. These are ellipsoid bodies with an opalescent transparency measuring 0.1 to 2 cm with a dense milky white spot at the side where the scolex remains invaginated. Man can also act as an intermediate host and harbor the cyst, which is termed as cysticercosis. In humans, ingestion of ova via improperly cooked pork, or food (vegetables)/water contaminated with eggs, or by autoinfection (either from contaminated hands or by reverse peristaltic movements) leads to cysticercosis. It is to be noted that infection can occur even in those who don’t eat pork via food prepared by an infected individual from an endemic region.

DIAGNOSIS

Clinical signs and symptoms

Systemic

Taeniasis causes only minor clinical problems in the form of gastrointestinal disturbances and pruritis ani. Cysticerci can be found in subcutaneous tissue, skeletal muscles, central nervous system, viscerae and eyes. Although only a mild tissue reaction occurs with a few viable cysticerci, heavy infestation can cause more marked generalized symptoms. Symptoms in cysticercosis occur mainly from invasion of the central nervous system (parenchymal, meningeal, ventricular and spinal). There could be mild neurological manifestations to severe epileptiform attacks, when the patient may fall and be injured. In neurocysticercosis, acute meningoencephalitic symptoms may ensue. Other symptoms include headache, lethargy, weakness, etc. Intracranial hypertension and hydrocephalous, and death may occur from blockage of the circulatory pathway of cerebrospinal fluid. Both living and calcified dead cysts cause neurological disturbances. Cysticerci can remain alive for 3 to 5 years. Subcutaneous nodules may be palpable.

Ocular

In and around the eye, the cyst can invade almost any ocular, orbital or adnexal tissue:

●Retina (subretinal or intraretinal);

●Vitreous;

●Orbit (extraocular muscle or retro-orbital space);

●Conjunctiva (subconjunctival);

●Eyelid;

●Optic nerve;

●Anterior chamber;

●Lens;

●Iris;

●Cornea; or

●Lacrimal gland.

Intraocular posterior segment cysticercosis, i.e. vitreal and subretinal, is a common occurrence. Cysticerci reach the subretinal space through posterior ciliary arteries, from where they migrate into the vitreous through a pre-existing retinal break or by perforating the retina, which usually seals with inflammatory reaction forming a chorioretinal scar. The parasite has a predilection for the macular region, presumably because of vascularity of the region (Figure 58.1a). The patient presents with a painless diminution of vision. The subretinal cyst may initially present as an acute retinitis with exudates and hemorrhages; peripheral cysticercus may be asymptomatic, or the patient presenting with floaters. The clinical picture of a translucent cyst in the vitreous with a scolex, which may be invaginated or evaginated, is unmistakable. Contractions and undulating movements of the cyst are often observed, more so on throwing ophthalmoscopic indirect light, when the scolex will invaginate (Figure 58.1b). As a reaction to the cyst, serous

a

b

FIGURE 58.1. Intraocular and orbital/adnexal cysticercosis. a) Subretinal cysticercus, seen as a black shadow (from masking of the background fluorescence) on this fluorescein angiogram. The macula is the preferred site because of vascularity of the area. There is an absence of inflammatory reaction at this early stage. The patient presents with a painless diminished vision initially (in this case of 4 days). b) Intravitreal cysticercosis having a dense white spot suggestive of the scolex.

Cysticercosis • 58 CHAPTER

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c

e

g

or exudative retinal detachment occurs (Figure 58.1c). Chorioretinitis, vitritis and severe anterior uveitis will often ensue; pain and redness from uveitis follows. Inflammation can cause tractional or combined tractional-rhegmatogenous retinal detachment; fibrous proliferations occur. Retinal detachment and proliferative vitreoretinopathy may form. Once the cyst dies its contents are spilled; the panuveitis secondary to release of toxins can lead to destruction of the globe and phthisis bulbi. Bilateral multiple cysticerci may be found.

106

d

f

FIGURE 58.1., cont’d c) Subretinal cysticercosis presents with a loss of vision; there is severe intraocular inflammation with an exudative retinal detachment. d) Orbital myocysticercosis. A child typically presents with proptosis, restricted ocular motility and redness. He is a vegetarian; the infection is commonly acquired through contaminated food in endemic regions such as India. On dextroversion, there is a restricted left eye movement. The cyst is present along the left lateral rectus, which was confirmed on CT scanning. This clinical picture is pathognomonic. e) A subconjunctival cysticercus, which will extrude out any time. It commonly extrudes spontaneously, the patient sometimes coming with the cyst in his hand. At times, this might have to be removed by giving a small cut on the conjunctiva and tenon’s capsule, when the cysticercus comes out along with a pus bead. f) Pseudo-retinal detachment. A solid-looking retinal elevation with striae caused by an orbital cysticercus, pushing the eyeball and indenting it. The patient presented with diminished vision in the presence of symptoms and signs of orbital inflammation. g) CT scan showing the cysticercus along the medial rectus, with an eccentric shadow of the scolex.

Extraocular muscle and subconjunctival tissue are the two commonest sites of presentation of extraocular/adnexal cysticercosis; involvement occurring probably through anterior ciliary arteries. These have been more common in reports from India. Extraocular muscle cysticercosis, the commonest form of orbital cysticercosis, typically presents with signs of orbital inflammation — a red eye, restricted ocular motility and/or proptosis. A painful inflammatory proptosis with restricted ocular motility when present in an individual with a history of

exposure to an endemic area is diagnostic of myocysticercosis. Though it occurs at any age, the majority of patients are usually children and young adults in their first two or three decades. The lesion excites a recurrent severe inflammatory reaction resulting in considerable pain accompanied by edema and chemosis. There is a decreased ocular motility in the direction of action of the involved muscle and a restriction of the opposite movement (diplopia) (Figure 58.1d). The presentation is characteristic and pathognomonic. A localized redness and nodule formation is present (Figure 58.1e). Although mentioned as two different primary sites, in our experience, subconjunctival cysts appear to be secondary to extrusion from extraocular muscles, which is the actual primary site. We have seen it in a large number of orbital cysticerci cases (49 patients) that myocysticerci are precursors of subconjunctival cysticerci, which finally extrude out spontaneously (Agrawal S, unpublished work, 2003). Involvement of levator palpebrae superioris results in ptosis. Superior oblique muscle cysticercosis may present as Brown syndrome. Myocysticerci cases usually have a single cyst with no systemic involvement. Bilateral/multiple cysts are rarely found.

At times, fundus appearance of a solid-looking retinal detachment caused by orbital cysticercosis mechanically indenting the eyeball can be seen, all the three coats of the eyeball pushed in from outside (very well supported by ultrasonography (USG) and computed tomography (CT) scan). The term pseudo-retinal detachment has been coined for it because it is not a true retinal detachment, there being no subretinal fluid. Retinal striae support the mechanical nature of the lesion (Figure 58.1f). Such patients present with diminished vision and associated signs of orbital inflammation — localized recurrent inflammation with conjunctival congestion, restriction of ocular movements and/ or proptosis.

Other forms are less common. Cysticercus may present with cranial nerve palsies, papilledema or optic neuritis. Rarely it can pass the vitreous and lens, and enter the anterior chamber, where it causes a severe anterior uveitis. The leucocytes in the anterior chamber are mostly eosinophils.

Investigations

The segments/eggs can be found in the fecal sample; perianal swabbing is important in diagnosis of taeniasis. An adult patient presenting with epilepsy for the first time should be suspected of having neurocysticercosis, especially with history of exposure to a hyperendemic area. These patients may have subcutaneous nodules (in 50%). Radiologic examination of the limbs and skull may show calcified cysts. Contrast-enhanced CT scan and magnetic resonance imaging (MRI) are required for brain and other lesions. USG may also be required for different visceral pathologies. Skin/subcutaneous nodule biopsy is diagnostic. Eosinophilia may be found in blood. Serological tests like indirect hemagglutination (IHA) (positive in 85% of patients and titers of 1 : 64 considered diagnostic) and complement fixation may be used; however, these cross-react with hydatid antigen, etc., and also give false positives in patients who only have adult worm infestation. A cerebrospinal fluid complement fixation test is more specific. ELISA (enzymelinked immunosorbent assay) for anticysticercus IgG is more sensitive but again cross-reacts with Taenia saginata/Echinococcus/Coenurus. Enzyme-linked immunoelectro transfer blot (EITB) assay is highly sensitive and specific (98%).

When clinical presentation suggests ocular cysticercosis but doubts arise (e.g. due to hazy media), diagnostic aids such as USG, CT scan or MRI are useful. Orbital/adnexal cysticercosis is conclusively diagnosed by these methods (Figure 58.1g) —

USG being most economical. Finding a cyst with an eccentric shadow of the scolex is pathognomonic. Fluorescein angiography may delineate a subretinal cyst. Aqueous humor tap can be screened for circulating antibody and antigen.

Differential diagnosis

Epilepsy, brain tumors, and other types of neurologic and psychiatric disorders may be simulated in neurocysticercosis. Diagnosis of ocular cases may be difficult in the presence of media haze from inflammation; in children different causes of leukocoria have to be ruled out. Orbital cases may present as cellulitis, pseudotumor or subconjunctival abscess.

PROPHYLAXIS

Infection is prevented by eating thoroughly cooked pork (56ºC for 5 minutes), properly washed and boiled vegetables, drinking clean water and by maintaining personal hygiene.

TREATMENT — MEDICAL AND SURGICAL

Systemic

Praziquantel (50 mg/kg/day) had been the drug of choice for taeniasis and cysticercosis. Albendazole (15 mg/kg/day) has been found to be more effective (penetrates better and achieves larvicidal concentrations) and cheap, and is fast replacing other drugs. Stools should be rechecked in 3 months. For cysticercosis, systemic removal of the cyst is recommended whenever possible. Destruction of the cysts in cerebral cysticercosis by anticysticercals may induce severe side effects from an inflammatory response. Corticosteroids (1.5 mg/kg/day) are used in these cases. Niclosamide (2 g) is another drug used. Old dead cysts are left as such. Asymptomatic subcutaneous nodules do not require treatment.

Ocular

The best course in cases of intraocular cysticercosis is the removal of the cyst by surgery, lest it causes irreversible damage. There has been concern of an exaggerated inflammatory response from release of toxins leading to destruction of the globe and phthisis bulbi following death of the parasite; hence antihelminthics are avoided. As a result of reaction to the cyst and its content, inflammation/exudative retinal detachment is often present. Corticosteroids are used to control the intraocular inflammation when present, and surgery should be performed under cover of steroids. Pars plana vitrectomy and removal of the intravitreal cyst should be undertaken at the earliest opportunity. The cyst can be aspirated into the port of the cutter — this requires care to be taken as it tends to shy away from the endoilluminator light. If the cyst is damaged, a thorough lavage of the vitreous cavity with fluid is in order to reduce the resulting severe inflammatory response. Subretinal cysts can be easily evacuated transvitreally by the vitrectomy procedure via retinotomy, or transclerally by giving a nick on the sclera over the base of the cyst (after it has been accurately localized), treatment of the scleral bed with diathermy and incision of the choroid, ensuring that the cyst has not moved during preparation of the site, with or without scleral buckling. Postoperatively, corticosteroids will have to be continued for a few weeks to suppress inflammation.

As with intraocular cysticercosis, it is better that the orbital cysts be extruded rather than killed inside. However, surgery

Cysticercosis • 58 CHAPTER

2 SECTIONDiseases Parasitic •

●When heavy infestation occurs, cuffing and formation of mite nests occur on the eyelashes.

Laboratory findings

Diagnosis of demodicosis is confirmed by the presence of parasites on epilated eyelashes. They can be identified when cilia are deposited in a droplet of saline on a slide and subjected to microscopy.

PROPHYLAXIS

●It is not known if the acarid is transmitted by personal contact.

●D. canis, which is taxonomically similar to D. brevis, produces mange in dogs and in earlier times was thought to be transferrable to humans.

TREATMENT

Ocular

Treatment consists primarily of lid scrubs using mild soap. Ether is not recommended. Topical antibiotics may be useful to alter lid flora and further reduce lid inflammation. Skin infestations may also be treated with topical acaricidal medications after facial washing on well-dried skin (crotamiton 10% in the morning and crotamiton 10% plus benzyl benzoate 12% in the evening). Simply washing the skin daily probably helps reduce the level of infestion considerably.

Systemic

Systemic therapy is used in demodectic management in canines with good effect. It is not recommended for humans.

COMMENTS

Demodicosis is associated with specific pathology of the eyelids. Demodex infestation is more common than is generally appreciated by the ophthalmic community. The degree to which it causes or contributes to ocular symptoms is still controversial and often difficult to determine unless the infestation is rather heavy. Demodectic mites have been recorded carrying Mycobacterium leprae bacilli and fungi, and this feature causes concern. Since treatment includes basic measures for treating blepharitis such as lid scrubs, the presence of mites in a symptomatic patient warrants treatment.

REFERENCES

Baima B, Sticherling M: Deomodicidosis revisited: Acta dermato-Venere- olog 82(1):3–6, 2002.

Bonnar E, Eustace P, Powell FC: The Demodex mite population in rosacea. J Am Acad Dermatol 28:443–448, 1993.

English FP, Cohn D, Groeneveld ER: Demodectic mites and chalazion. Am J Ophthalmol 100:482–483, 1985.

English FP, Zhang GW, McManus DP, Campbell P: Electron microscopic evidence of acarine infestation of the eyelid margin. Am J Ophthalmol 109:239–240, 1990.

Erbagci Z, Erbagci I, Erkilic S: High incidence of dermodicosis in eyelid basal cell carcinomas. Int J of Dermatol 42(7):567–571, 2003.

Forton F, Germaux MA, Brasseur T, et al: Demodicosis and rosacea: epidemiology and significance in daily dermatologic practice. J Am Acad Dermatol 52(10):74–87, 2005.

Karincaoglu Y, Bayram N, Aycan O, Esrefoglu M: The clinical importance of Demodex folliculorum presenting with nonspecific facial signs and symptoms. J Dermatol 31(8):618–626, 2004.

Kemal M, Summer Z, Toker MI, et al: The prevelance of Demodex folliculorum in blepharitis patients and the normal population. Ophthalmic Epidemiology 12(4):287–290, 2005.

Smith S, MaCullough C: Demodex folliculorum palpebrarum. Can J Ophthalmol 4:3–15, 1969.

Wolf R, Ophir J, Avigad J, Lengy J, Krakowski A: The hair follicle mites (Demodex sp.). Acta Dermatol Venereol (Stockholm) 68:535–536, 1988.

60 ECHINOCOCCOSIS 122.9

F. Hampton Roy, MD, FACS

Little Rock, Arkansas

ETIOLOGY/INCIDENCE

Echinococcosis is an infection caused by the larval forms of the genus Echinococcus. E. granulosus is the most common of the species, which also includes E. multilocularis, E. oligoarthus and E. vogeli. The worms of all species live in the intestines of the host, which is usually a dog. The human acts as an intermediate host, becoming infected by ingestion of the eggs of the organism through contaminated food or water. Eggs hatch in the intestines, and the embryos penetrate the intestinal wall to gain the portal to circulation. The parasite forms a vesicle containing fluid in the internal organs, which is called a hydatid cyst; the disease is called hydatid disease. Usually only one slowly growing cyst develops, but it may persist for many years.

The hydatid cyst has an outer acellular laminated membrane and an inner germinative layer. The outer (or cuticular) layer is surrounded by an adventitial layer that is a granulamatous reaction produced by the host. Secondary cysts (brood capsules) bud from the germinative layer, in which protoscoleces are produced. Accidental rupture of the cyst may give rise to anaphylactic reactions.

DIAGNOSIS

Clinical signs and symptoms

Clinical manifestations are determined by the locations of the cysts. The liver is the most common site for hydatid disease, accounting for 60% to 70% of cases. The pulmonary form is found in about 30% of cases. Less frequently, the spleen, kidney, central nervous system, or heart may be involved.

Only 1% of cases of echinococcosis may have an ophthalmologic location, which is usually situated in the orbit. Few cases of anterior chamber, vitreous, or subretinal cysts have been reported. Orbital hydatid cysts are more commonly found in young adults. Patients present with progressive, unilateral, nonpulsating exophthalmos with a duration of approximately 1 month to 2 years. The cysts tend to be located superiorly and may erode the orbital roof, invading the cranial cavity. Pain may be present, as well as ocular motion restriction, papilledema, and retinal striae. Advanced cases may present conjunctival chemosis, lid edema, and exposure keratitis.

Echinococcosis • 60 CHAPTER

2 SECTIONDiseases Parasitic •

Laboratory findings

Hydatid cyst should be included in the differential diagnosis of unilateral proptosis in patients from countries where echinococcosis is endemic.

●Plain orbital radiographs may show enlarged orbital diameters and increased soft-tissue density.

●Ultrasonography demonstrates a cystic lesion without internal reflectivity.

●Computed tomography discloses a well-defined cystic mass.

●Magnetic resonance imaging reveals a low-intensity signal on T1-weighted images and a high-intensity signal on T2-weighted images.

●Because of the integrity of the cyst, serologic tests (like the detection of arc-5 antigen) may be negative in orbital hydatid disease.

TREATMENT

Medical

Medical treatment of echinococcosis is usually carried out in patients for whom surgery cannot be performed or in cases in which the cyst has ruptured. Mebendazole or albendazole is used in these cases.

Surgical

The treatment of choice for orbital hydatidosis is surgical. Various surgical approaches can be used, although lateral osteoplastic orbitotomy (the Krönlein–Berke procedure) is the most common. Once the cyst is observed, puncture and aspiration of its liquid content is performed. The content of the cyst is replaced with 1% formaldehyde in saline, hypertonic solution, or 70% alcohol and is left in place for 5 minutes, followed by surgical excision of the parasitic membrane and its contents.

COMMENTS

Although echinococcosis may occur throughout the world, it constitutes a major health problem in particular areas. E. granulosus has a worldwide distribution, with high incidence in North Africa, the Middle East, Australia, South America, and certain rural areas of central Utah, California, New Mexico and Arizona in the United States. E. multilocularis is more frequent in Central Europe, whereas E. oligarthrus and E. vogeli are found in Central and South America. Preventive measures should include education of the public in order to eliminate the feeding of infected waste materials to dogs. Contact with infected dogs should be avoided, and treatment of these animals should be instituted.

REFERENCES

De Silva N, Guyatt H, Bundy D: Antihelmintics: a comparative review of their clinical pharmacology. Drugs 53:769–788, 1997.

Ergun R, Okten AI, Yuksel M, et al: Orbital hydatic cysts: report of four cases. Neurosurg Rev 20:33–37, 1997.

Fry G: Anti-helminthic therapy. Curr Opin Infect Dis 10:461–465, 1997.

Gomez Morales A, Croxatto JO, Crovetto L, et al: Hydatic cyst of the orbit: a review of 35 cases. Ophthalmology 95:1027–1032, 1988.

Jones TC: Cestodes. In: Mandell GL, et al, eds: Principles and practice of infectious diseases. Edinburgh, Churchill Livingstone, 1990:2155–2156.

Lerner SF, Gomez Morales A, Croxatto JO: Hydatic cyst of the orbit. Arch Ophthalmol 109:285, 1991.

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61 OCULAR TOXOCARIASIS 128.0

Carlos Walter Arzabe, MD

Santa Cruz, Bolivia

ETIOLOGY/INCIDENCE

Two nematode larvae can cause toxocariasis. Both are round worms found in the intestine of dogs (T. canis) and cats (T. cati). Eggs eliminated in the feces of these animals are not infective and require an incubation period in the soil to embryonate, in which they can remain latent and infectious for many years. Puppies usually contract the T. canis from the mother before birth or from her milk. When the puppies are 3–4 weeks old, produces large number of eggs that contaminates the environment through their feces. Warm, humid climates help survival of eggs in the soil. Patients can become infected after accidentally swallowing infective Toxocara eggs from contaminated soil or feces.

Toxocariasis is one of the most commonly reported zoonotic helminth infections in the world. It may develop at any age, although the initial infection typically occurs in childhood, because young children’s are more likely to ingest the eggs of the worm from contaminated soil or by their permanent contact with infected puppies that have not been dewormed. Consequently, toxocariasis is found more commonly in individuals who have contact with soil, e.g. children and farmers.

T. canis L3 larvae deposit excretory-secretory (ES) antigens in the eye. The ES antigen activates complement, attracts eosinophils, and stimulates T cells and other immune cells. Acute inflammation develops around the parasite or deposited ES antigen. The inflammatory response can lead to retinal detachment with visual loss.

DIAGNOSIS

Clinical signs and symptoms

There are three main clinical forms of the disease:

1.Symptomatic visceral larva migrans is caused by the host response to parasite-excreted surface antigen dropped by the larvae during their migration through the body. It is characterized by fever, irritability, pallor, anorexia, malaise, eosinophilia, hepatomegaly, coughing, asthma or pneumonia. Is a disease of young children (6 months–4 years of age). Fortunately, most systemic infections are mild and produce no serious morbidity.

2.Covert toxocariasis is a syndrome characterized by abdominal pain, anemia and eosinophilia.

3.Ocular toxocariasis is the least common presentation of toxocariasis. Eye involvement is usually unilateral, with bilateral lesions occurring in only 1%.

Laboratory findings

Eosinophilia is usually present in patients with visceral diseases but often absent in patients with ocular infection.

ELISA test is the test of choice to document systemic or ocular infection with T. canis. It is particularly useful for the diagnosis of visceral disease, in which antibody titers tend to be high. In contrast, in ocular disease, antibody levels are significantly lower according to the Centers for Disease Control, and a serum titer of 1 : 8 is sufficient to support the diagnosis if the patient has signs and symptoms compatibles with ocular toxocariasis.

ELISA testing of intraocular fluids (vitreous and aqueous humor) is of great value in the diagnosis.

Standardized echography can be of help in the diagnosis of this ocular disease.

In the ocular form, one or more larvae become trapped in the eye, causing a granuloma in the retina. This nematode may be located beneath or within the retina, or may extend into the choroid and vitreous.

●Posterior pole ‘granuloma’ (usually, patients with 6–14 years old).

●Peripheral granuloma (with a quiet eye, range in age from 6–40 years old).

●Children with diffuse chronic endophthalmitis (usually, patients with 2–9 years old).

●Uveitis.

●Unilateral pars planitis.

●Macular scarring.

●RPE changes.

●Retinal detachment.

The nematode it may remain viable for several years in the eye.

In many instances, the child does not present for medical attention until permanent ocular damage has taken place. (See Figure 61.1.)

The nematode may enter the eye via central retinal artery (peripheral granuloma), or via the short posterior ciliary arteries (optic disc, macula or posterior pole).

Differential diagnosis

●Retinoblastoma.

●Retrolental fibroplasia.

●Familial exudative vitreoretinopathy.

●Coats’ disease.

●Persistent hyperplastic primary vitreous.

●Pars planitis and other uveitis.

PROPHYLAXIS

Education is important. Wash hands often, especially after playing with a pet.

Dogs and cats should be dewormed regularly, starting before they are 4 weeks old.

Dogs release T. Canis in their stool. A single dog feces can contain approximately 1 million eggs. The eggs are resistant and can survive for over 10 years. Freshly deposited feces are not infectious and can safely removed. Toxacara eggs become

FIGURE 61.1. A 15-year-old boy with a localized, white, elevated peripheral ‘granuloma’ caused by Toxocara canis, and typical fibrocellular stalk running to the optic nerve, as well as the macular area in which a macular ectopia and dragging of the macular vessels has developed due to the transvitreal traction bands.

infectious when they embryonate, this is usually 2–3 weeks after they have been deposited by the dog.

TREATMENT

The natural history of toxocariasis is to resolve spontaneously over a period of weeks to months, so visceral larva migrans often is treated conservatively. If treatment is necessary, 5 mg/kg albendazole b.i.d. can be used. Diethylcarbamazine has been recommended by some.

Treatment of the inflammatory stage of the ocular disease is with antinflamatory/cycloplegic eye drops, and periocular depomethylprednisolone (40–60 mg), repeated every 7–14 days until the process resolves itself.

If antihelminthic therapy is used, it should always be coupled with steroids because T. canis, is not a self-replicating organism. A common combination is Thiabendazole, 500 mg PO q.i.d. or 20 mg/kg/day in divided doses for 5 days; plus 40 mg of prednisone PO qd for 10 days tapered as warranted by the rate of resolving intraocular inflammation.

Surgery may be indicated to manage the complications of ocular toxocariasis, including repair of retinal detachment. Detachment is usually caused by vitreous bands that can be removed only by vitrectomy. Vitrectomy may also be indicated to remove the opaque vitreous secondary to inflammation.

Cryocoagulation and photocoagulation also kill the larvae effectively but should not be used within the foveal area.

Toxocariasis Ocular • 61 CHAPTER