TABLE 1. Protozoal Infections of the Eye or Adnexa

TABLE 2. Helminthic Infections of the Eye or Adnexa

Cell-mediated immunity and humoral immunity play important roles in the defense mechanisms against parasitic infections.³ The same mechanisms may also participate in tissue damage.⁴ Parasites often establish mechanisms that permit survival in the host. Some parasites undergo antigenic alteration in their surface membrane, allowing them to evade the immune response of the host. Other parasites secrete minimal antigen, thus evoking little host reaction or immune tolerance. Some parasites produce substances that cause an inhibition of macrophage activity. In certain instances (e.g., Toxoplasma), parasites can cause immunosuppression of the host or may escape the immune mechanisms of the host by forming cysts within the tissue. The cyst wall may be composed of an outer layer from the host's own tissue, thus escaping recognition by the immune system.⁵

The outcome of parasitic infection depends on the parasite itself and the immune status of the host. The natural defense mechanisms of the host may be compromised by disease or therapy. Parasitic infections that commonly occur in patients with acquired immunodeficiency syndrome (AIDS) include toxoplasmosis, pneumocystosis, microspori(diosis, cyclosporiasis, isosporiasis, cryptosporidiosis, and disseminated strongyloidiasis.¹

PHYLUM SARCOMASTIGOPHORA

The phylum Sarcomastigophora is divided into two subphyla: the Sarcodina, or amebae, and the Mastigophora, or flagellates. The ameboflagellates are a group of organisms that have the characteristic of both the amebae and the flagellates. The Sarcodina subphylum contains those forms that move by pseudopodia and includes all free-living amebae, as well as those that are symbiotic in the intestinal tract and elsewhere in the body. This subphylum contains the entamebae and Acanthamoeba organisms. Mastigophora is a subphylum of a group of organisms that have specialized structures known as the flagella. Flagella arise from small intracytoplasmic granules known as blepharoplasts that help to propel the organism. The location and number of flagella may vary from one species to another.

PHYLUM APICOMPLEXA

Members of phylum Apicomplexa have a complex life cycle, with a reproduction characterized by sexual and asexual phases. The genera in this group of parasites include the Plasmodium, which is the cause of malaria, and species of the genera Isospora, Cryptosporidium, and Sarcocystis, which are parasites of the intestinal mucosa; and Toxoplasma, Pneumocystis, and Sarcocystis, which are found as parasites of tissues and organs.

PHYLUM MICROSPORA

The phylum Microspora includes a group of parasites that used to be classified under Protozoa. Microspora are tiny intracellular parasites that may infect vertebrates and invertebrates. Microsporida are becoming important cause of morbidity in immunocompromised persons and AIDS patients.

PHYLUM CILIOPHORA

The phylum Ciliophora includes a variety of free-living and symbiotic species. The organisms have cilia, which are structurally similar to flagella but are shorter and more numerous. An example of these parasites is Balantidium coli, which is found in the intestinal tract. These organisms do not cause significant ocular disorders.

PHYLUM PLATYHELMINTHES

The phylum Platyhelminthes, or flatworms, contains parasites that are flat and have a symmetric body. Most of these flatworms have both male and female reproductive systems. The adult worm may range in length from 1 mm to several meters. Most members of this phylum live either on or in the body of their host. The trematodes (flukes) and cestodes (tapeworms) exist in parasitic form only. The trematodes are elongated, slender organisms that attach to the host tissue with hooks or cup-shaped muscular depressions called suckers. They have a simple digestive tract. Members of the class Cestoda have a ribbonlike, elongated, segmented body and an anterior specialized attachment organ, or scolex. They have no digestive system. Adult cestodes inhabit the small intestines. Intermediate hosts are required for the development of cestodes.

PHYLUM ASCHELMINTHES

The phylum Aschelminthes contains the nematodes, or roundworms, which are elongated and cylindrical in shape. Each worm is either male or female (i.e., the sexes are separate), and the male is frequently smaller than the female. A welldeveloped digestive tract is present. Intermediate hosts are necessary for the larval development of their forms. Some of the nematodes are free living, but a large number of species are parasitic to humans and animals.

PHYLUM ACANTHOCEPHALA

Worms in the phylum Acanthocephala are endoparasitic and have modified hooks and a retractable proboscis to facilitate attachment. The heads are thorny. The cycle requires an intermediate host. The sexes are separate, and the male is smaller than the female.

PHYLUM ARTHROPODA

The phylum Arthropoda contains parasites that have jointed, paired appendages (“feet”). They have a tough, chitinous exoskeleton, a symmetric body, and a well-developed digestive tract. The sexes are separate. There are several classes in this phylum, many of which are of medical importance. Some genera cause parasitic infections of the eye (e.g., Pediculosis, Myiasis), produce venom, cause damage to the tissues, or can be fatal. Arthropods may serve as vectors for infectious organisms, yet others provide shelter for parasites or serve as intermediate hosts for the development of other parasites.

PHYLUM PENTASTOMIDA

The parasites in the phylum Pentastomida are endoparasites. They can cause diseases of the lungs, but they do not usually produce ocular disease.

MICROSPORIDIOSIS

Microsporidiosis is an infection caused by the obligate intracellular parasite of the order Microsporida. The four principal genera that may produce disease in man are (1) Pleistophora, (2) Nosema, (3) Encephalitozoon, and (4) Enterocytozoon. Because these parasites are tiny, they stain poorly in tissue sections and show little tendency to produce inflammatory reactions in the tissues. The organisms are difficult to identity, and subclinical infections are common. Most human cases of microsporidiosis have been reported in children, immunodeficient persons, and AIDS patients.^6–11

The organism belongs to the phylum Microspora, class Microsporea, and order Microsporida. The two suborders are Pansporoblastina and Apansporoblastina. The first sporulates in the host cell with the sporocyst, and the latter lacks a pansporoblastic membrane. The Pleistophora species belongs to the suborder Pansporoblastina, whereas the Nosema, Encephalitozoon, and Enterocytozoon species belong to the suborder Apansporoblastina.¹

Microsporida are, as mentioned, obligate intracellular parasites. They are characterized by two developmental stages inside the host cell: (1) the feeding, or schizogenic, stage; and (2) the sporulation, or sporogenic, stage.

Microsporida may vary in size from 1 to 18 μm in length, but most pathogenic organisms are approximately 2 μm in size. The spores of Microsporida are oval or spheric, and each spore consists of sporoplasm with a polar filament and varying numbers of coils and tubules, depending on the species. The existence of a polar filament identifies the organism as microsporidian.¹² The infection is transmitted by the fecal-oral route. In corneal infection, direct inoculation may be responsible for the disease and the keratitis.^13,14 The most common ocular manifestation of microsporidiosis is keratitis.¹¹ Several cases of microsporidiosis have been reported in association with AIDS. Patients with microsporidiosis present with conjunctival hyperemia, irritation, photophobia, and foreign-body sensation. Involvement of the cornea may lead to a decrease in vision. Conjunctival hyperemia and edema are associated with papillary hypertrophy. Biomicroscopy of the cornea shows tiny, punctate epithelial keratitis.^7,11 The diagnosis of corneal and conjunctival involvement may be confirmed by corneal scrapings or by obtaining biopsy specimens, which are then subjected to electron microscopic studies.¹² These organisms may not be visible on routine microscopy. With a hematoxylin and eosin stain, the Microsporida organisms may appear refractile, having a clear cytoplasm and basophilic nucleus that makes it hard to identify.¹⁴ Giemsa staining may be helpful. The organisms have variable staining with acid-fast stain and appear to be gram-positive. The cell wall stains with Gomori methenamine silver (GMS) stain. The polar granule of Microsporida can be demonstrated by periodic acid-Schiff (PAS) stain.

Electron microscopy shows typical coiled polar filaments with one or two nuclei in the sporoblast and spores. Several nuclei are seen in the schizont. These stages do not show mitochondria. The organism may be differentiated from other protozoa, such as Toxoplasma, Leishmania, and Cryptosporidium. For example, Toxoplasma is larger (approximately 6 to 7 μm in length) and does not stain with GMS. Leishmania does not stain with GMS and is larger than Microsporida. Cryptosporidium is similar to Microsporida in size, but is found extracellularly and does not invade the cells. Serologic tests for microsporidiosis are available, including enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescent assay, but the sensitivity and specificity of these tests have not been established. The most frequently encountered genus causing microsporidiosis in patients with AIDS is Encephalitozoon. Several species have been identified. A species of Microsporida, Encephalitozoon hellem, has been isolated from a patient with disseminated microsporidiosis. The organism is thought to be the same organism as has been found in the cornea of several AIDS patients with keratoconjunctivitis.

The diagnosis of Microsporida keratitis is made on the basis of clinical findings by slit-lamp biomicroscopy, which in immunocompromised patients typically shows multiple intraepithelial white-gray opacities throughout the epithelium. Confocal microscopy and the chromotrope stain may allow rapid confirmation of the diagnosis and the initiation of therapy.¹⁵ The diagnosis is confirmed by examining corneal scrapings, which show organisms within the epithelial cells. These organisms measure 1 to 2 μm in length and contain PAS-positive anterior granules. Diagnosis can also be made by examining conjunctival scrapings. This has been facilitated by the use of immunofluorescein techniques using antisera against Encephalitozoon hellem. The scrapings usually do not show evidence of inflammatory reaction, and epithelial cells are seen containing the organisms. In conjunctival tissue, biopsy specimens of inflammatory cells may be seen, and the organisms are normally present within the conjunctival macrophages.

Immunocompetent patients with microsporidiosis recover after an asymptomatic course, and the disease may be self-limited. The treatment of microsporidiosis in AIDS patients can be difficult because available drugs are not highly effective. Treatment includes the topical use of fumagillin (Fumidil B).¹⁶ Fluconazole may be used as an alternative therapy in patients with microsporidiosis.

GIARDIASIS

Giardiasis is caused by the protozoan Giardia lamblia. The disease has a worldwide distribution and is considered to be a leading cause of intestinal parasitic disease. Giardiasis may occur in the absence of clinical signs and symptoms, and the parasite may stay in the intestines in a subclinical form. The parasite is transmitted through the fecal-oral route. Drinking water is the most common mode of transmission. Person-to-person transmission has been reported in day care centers and among homosexual men.

The trophozoites of G. lamblia are pear-shaped and measure 8 to 20 μm in length and 5 to 15 μm in width. The organism has two nuclei with prominent karyosomes, and four pairs of flagella with two ventral suckers. The cyst of the parasite is oval and measures 10 to 20 μm in longest diameter. Each cyst has four nuclei but does not possess flagella or suckers. Upon excystation, the organism becomes a trophozoite with two nuclei and starts dividing by binary fission.

The most frequently encountered clinical symptoms are recurrent episodes of diarrhea, malaise, weakness, abdominal distention and cramps, nausea, vomiting, anorexia or weight loss, fever, and occasional constipation.

The ocular manifestations appear to be secondary to hypersensitivity reactions to Giardia antigen. The ocular manifestations that have been reported include anterior uveitis, choroiditis, and hemorrhagic retinopathy. The correlation between ocular manifestations and intestinal giardiasis has been circumstantial. Several patients have reported improvement in their ocular symptoms after being treated for giardiasis. The presumptive association between giardiasis and ocular manifestations has been met with skepticism. Mantovani and associates¹⁷ studied 90 children in Italy with symptomatic giardiasis, 10 of whom had ocular manifestations. Eight of these children presented with a diffuse salt-and-pepper appearance of the fundus with retinal pigment epithelial involvement in the midperiphery in both eyes. In 1 of the 8 children, atrophic areas of the retinal pigment epithelium were noted as well as small, hard exudates in one eye. Of the remaining 2 children, 1 had evidence of chorioretinitis, and the other had hyperemia of the optic nerve head. After therapy with tinidazole 50 mg/kg (single dose), patients were followed up for 1 year. The child with chorioretinitis recovered after treatment with systemic corticosteroids, and the retinal pigment epithelial changes in the other patients remained the same. The results were compared with healthy children: none of the 200 children with gastrointestinal symptoms that were unrelated to giardiasis had evidence of salt-and-pepper changes in the fundus. Ocular manifestations that were observed in the giardiasis group were not observed in any of the control groups.

Treatment of giardiasis includes the administration of tinidazole, furazolidone (Furoxone), metronidazole (Flagyl), or quinacrine hydrochloride (Atabrine).

PNEUMOCYSTOSIS

Pneumocystosis is a disease caused by species of the genus Pneumocystis. The organism found in rodents, however, differs ontogenetically from the species found in man.

The organism is a recognized cause of pneumonia in infants and immunocompromised patients. In the last quarter of the twentieth century, there was an increase in the incidence of Pneumocystis carinii pneumonia, partly because of the increase in AIDS cases.^18–32 In AIDS, Pneumocystis carinii pneumonia is probably the result of reactivation of a latent subclinical infection.

Pneumocystis carinii has been classified as a protozoan, but the taxonomic classification of the organism has been the topic of debate for many years. Pneumocystis is regarded as a protozoan because it enters both a cyst stage and the trophozoite stage during development. The organism possesses pseudopodia and can attach to the host cell. Previous studies, including ribosomal RNA-sequencing studies, have indicated that Pneumocystis is closer to fungi than to protozoa. Three developmental stages of this organism have been recognized: precyst, cyst, and trophozoite. The cyst has a thick wall and contains eight sporozoites (intracystic bodies). After excystation, the sporozoites become trophozoites. The trophozoite measures 1.5 to 5 μm in length. It has two cell membranes, which measure approximately 25 nm. The cellular contents of the organism include a nucleus with a rough endoplasmic reticulum, vacuoles, a round body, and mitochondria. On electron microscopy of clinical specimens, the trophozoite appears as a round structure. The cyst wall consists of three layers and measures approximately 0.25 μm in thickness. The inner surface of the wall demonstrates focal thickening, having parenthesis-shaped inclusions that can stain with a silver-containing stain such as GMS. The sporozoite measures approximately 1 to 1.5 μm in diameter and contains the same organelles as the trophozoite.

The Pneumocystis carinii may cause interstitial pneumonia in the immunocompromised host. Kwok and colleagues³³ identified Pneumocystis organisms in the area of cotton-wool spots in a patient with AIDS. The report of this association, however, has been questioned because the organism did not take the silver stain, the intracystic bodies contained no nuclei, and no cyst wall could be demonstrated by electron microscopy.³⁴ Choroiditis in patients with AIDS has been suggested to be caused by Pneumocystis carinii. Freeman and co-workers³⁵ reported on Pneumocystis carinii choroidopathy. Clinical, histopathologic, and electron microscopic studies of Pneumocystis carinii choroiditis have been reported by Rao and associates.³⁶

The diagnosis of pneumocystosis is confirmed by studying tissue biopsy specimens. Sputum specimens may be examined for screening purposes. Immunofluorescence stain is used with monoclonal antibodies specific for Pneumocystis carinii. GMS is a stain of choice for the diagnosis of pneumocystosis because of its ability to demonstrate the parenthesislike inclusions that are localized thickening in the inner surface of the cyst wall. The inclusions are parenthesis in shape, representing focal thickening in the inner surface of the cyst wall. Giemsa stain may be used to demonstrate sporozoites arranged in a halo within the cyst. Excysted sporozoites may appear as artifacts by Giemsa stain. A routine use of Giemsa stains is not recommended because they appear like artifacts and cannot be distinguished. Hematoxylin and eosin stain does not demonstrate Pneumocystis well. In GMS-stained slides, Cryptococcus can resemble Pneumocystis; a positive stain with mucicarmine and the budding cells will further distinguish the capsule of Cryptococcus from Pneumocystis. Pneumocystosis is treated with a combination of trimethoprim and sulfamethoxazole.

TERRAMEBIASIS

Terramebiasis is caused by soil amebae belonging to the genera Naegleria and Acanthamoeba. Naegleria fowleri causes primary amebic meningoencephalitis, which can be fatal, whereas Acanthamoeba species may cause amebic keratitis.^37–42

These forms of ameba include free-living and parasitic forms. Some of the free-living amebae can exist in either independent or parasitic forms. Naegleria and Acanthamoeba species live freely in the soil and have been isolated from the stagnant water of lakes, ponds, and hot springs, as well as from stagnant fresh water lakes. Naegleria infection is transmitted to humans by swimming in contaminated water. Naegleria is believed to invade the nasal mucosa during swimming and can penetrate the cribriform plate and ultimately infect the subarachnoid space, leading to meningoencephalitis. There has been no reports on ocular involvement with Naegleria species. In patients with amebic keratitis, the portal of entry is the eye, which follows direct exposure to contaminated water or solutions. Patient may give a history of minor trauma to the eye, followed by washing the eye with contaminated water. The recent increase in the incidence of amebic keratitis is predominantly due to the wide use of contact lens solutions. The use of tap water to make homemade contact lens solution has contributed to this problem. The use of topical corticosteroids may enhance the corneal invasion by the organism.

Common causative agents of Acanthamoeba keratitis are Acanthamoeba polyphaga and Acanthamoeba castellani and, less commonly, Acanthamoeba culbertsoni and Acanthamoeba rhisodes.

Naegleria and Acanthamoeba have two developmental stages: (1) trophozoite and (2) cyst. The trophozoite becomes encysted when there is a change in the environmental food supply, pH, or accumulation of waste products. When conditions become more favorable for excystation, the ameba digests the mucoid plug that seals the pore of the cyst and proceeds to squeeze its way out through the pore. Naegleria is an ameba with flagella and a single blunt pseudopodium, which distinguishes it from Acanthamoeba species. The trophozoites of Acanthamoeba species measure 15 to 45 μm in length and have thornlike pseudopodia and a lobopodium. The most characteristic structure is the vesicular nucleus, which has a large, centrally located karyosome. The cytoplasm contains coarse granules and contractile vacuoles. In tissue section, the Acanthamoeba assumes a size measuring 8 to 15 μm and has vacuolated cytoplasm. The cyst of Acanthamoeba measures 9 to 27 μm and has a wrinkled, round wall. During invasion of the cornea, the trophozoites invade the damaged cornea, leading to chronic keratitis. Patients with Acanthamoeba corneal infection have a history of minor trauma with direct exposure to contaminated water or contact lens wear. Patients complain of blurring of vision, discomfort, and irritation. Patients may complain of severe pain that is more prominent than the clinical findings. On biomicroscopy, patients have marked conjunctival hyperemia. The cornea shows evidence of chronic, indolent keratitis, which may be misdiagnosed as herpetic infection because of the dendritiform appearance of the lesion.⁴² Early cases show superficial epithelial keratitis with nummular subepithelial keratitis. As the condition progresses, the infiltrate involves the stroma, leading to a ring stromal infiltrate.³⁸ Ulceration and subepithelial infiltration may also develop. Another clinical manifestation of Acanthamoeba keratitis is perineural infiltration, or keratoneuritis.³⁹ The absence of vascularization is striking despite intense or prolonged keratitis. Scleritis may complicate the keratitis as well as uveitis.⁴² A small hypopyon may form. The condition may become refractory to topical therapy. Confocal microscopy has been used in the diagnosis of Acanthamoeba keratitis.⁴³

Acanthamoeba can be cultured from corneal scrapings on 1.5% nonnutrient agar layered with Escherichia coli. The trophozoite has a characteristically large nucleus and a single contractile vacuole. These are easily seen when stained with Wheatley's trichrome or Heidenhain-iron-hematoxylin-eosin stain. Acanthamoeba sp. grow in a complex defined growth medium containing amino acids, trace elements, vitamins, and salts. Acanthamoeba cysts can form in monolayer cultures on synthetic media by glucose-acetate starvation.⁴⁴ The cyst is resistant to most chemotherapeutic agents. Acanthamoeba is cultured on plates incubated at 37°C to 42°C in an anaerobic environment and examined at 24-hour intervals for the presence of amebic trophozoites and cysts. The plates can be examined microscopically at 10X magnification. Placing the Naegleria species in buffer solution can induce formation of the flagella.

Acanthamoeba can be stained with Gram's, Giemsa, GMS, and PAS stains. Trichrome, Giemsa, GMS, and PAS stains can be used for tissue-section staining as well. The cysts and trophozoites of Acanthamoeba species in tissue sections can be differentially stained with calcofluor-U (Hemo-De). Because Acanthamoeba trophozoites rupture rapidly in air-dried smears and corneal scrapings, such preparation should be stained promptly. Indirect immunofluorescent tests can be used to identify the organism. Immunoperoxidase staining is preferable for tissue sections. Other commercial products are available for the diagnosis of Acanthamoeba, such as Hemacolor and the chemofluorescent dye Cellufluor.

Management of Acanthamoeba keratitis remains a challenging clinical problem.⁴² Many types of topical therapeutic modalities have been tried but have had limited success. Failure has probably been due to their inefficacy against the cyst of Acanthamoeba; however, many types of topical medications may be effective against the trophozoite, including neomycin, propamidine, isethionate, dibromopropamidine, paromomycin, and imidazole (e.g., miconazole, itraconazole, fluconazole).³⁷ Recently polyhexamethylene biguanide (a disinfectant) and chlorhexidine have been used successfully in the treatment of Acanthamoeba keratitis.^45,46 Chlorhexidine (0.02% eyedrops) has been shown to be safe and effective in the treatment of Acanthamoeba keratitis. Topical corticosteroids should be avoided. Surgical intervention and corneal transplantation may be indicated in patients with severe corneal lesions or corneal perforations.^41,42

LEISHMANIASIS

Leishmaniasis is a widespread protozoan disease caused by the genus Leishmania. The disease is transmitted by the sandfly. The disease manifests clinically in two forms: (1) visceral and (2) cutaneous. The ocular lesions involve the eyelids, cornea, and anterior uvea.^47–49 Table 3 shows the classification of leishmaniasis and the taxonomy of the parasites in endemic areas.

TABLE 3. Leishmaniasis

Leishmania species are morphologically indistinguishable, but they can be classified on the basis of behavior, clinical manifestations, epidemiology, and insect vectors, as well as by growth characteristics in culture medium and by the immunologic reactions of the host. Leishmania occurs as amastigote in the vertebrate host and as promastigote in the invertebrate host and in tissue cultures. The amastigotes are small, oval protozoa with flagella. The promastigote form is equipped with a long, delicate anterior flagellum. Reproduction occurs by binary fission. The life cycle of the organism involves an alternating existence in a vertebrate and an insect host. Humans and domesticated and wild animals serve as natural reservoir hosts. The invertebrate hosts are the sandflies Phlebotomus and Lutzomyia. Promastigotes develop in the gut of the insect after a blood meal and mature to an infective form that migrates toward the pharynx.¹ Transmission takes place when the insect bites a host. When the flagellate promastigote gains access to a human, it loses its flagellum and assumes the amastigote form. The organism multiplies within macrophages and polymorphonuclear cells and in cells of the reticuloendothelial system. Skin infections in humans are caused by Leishmania tropica and Leishmania brasiliensis as well as Leishmania major, Leishmania guyanensis, Leishmania panamensis, and Leishmania pifanoi. The host for Leishmania tropica and Leishmania major is the desert gerbil Rhombomys opimus, and the skin lesions are mostly on the ears. Leishmania tropica can cause cutaneous lesions in dogs. Leishmania aethiopica may lead to skin lesions in the hyrax, a rodent found in highland areas in Ethiopia and East and South Africa. Leishmania tropica is the parasite that causes skin lesions in humans; in the Middle East, these lesions are known as the Oriental sore, Aleppo button, or Delhi boil.

Following the bite of the sandfly, the parasite gains access to the superficial corium of the skin and overlying epidermis, producing a focal, chronic, ulcerated granuloma. The lesion may remain ulcerative for weeks or months. Leishmania brasiliensis represents the South American counterpart of Leishmania tropica and Leishmania major. Leishmania brasiliensis infections may begin near the eyelids and at the canthal edges. The most frequent site of infection by Leishmania brasiliensis is the nares of the mucocutaneous junction. The eroding ulcer at the nose may destroy the cartilage and the septum leading to espundia. The major ocular manifestations of cutaneous leishmaniasis include ulcers of the eyelids leading to ectropion.^49,50 In some patients, phlyctenular and nummular keratitis have been observed, which appears to be because of a hypersensitivity reaction to the Leishmania antigens.⁴⁹ Nummular and phlyctenular keratitis respond to topical treatment with corticosteroids.

Diagnosis of leishmaniasis can be confirmed by laboratory tests, smears, or tissue biopsy specimens. Giemsa stain smears or hematoxylin and eosin-stained biopsy specimens may demonstrate the organism. Giemsa and Wilder's reticulum stain may also help identify Leishmania bodies in biopsy specimens. The serologic test frequently used is a direct immunofluorescent antibody test using formalinized promastigote Leishmania obtained from culture. ELISAs have also been shown to be sensitive and specific for Leishmania. ELISA testing for Leishmania antigen may cross-react with sera from cases of lepromatous leprosy, tuberculosis, and African trypanosomiasis.

Treatment of visceral leishmaniasis consists of intramuscular injections of stibogluconate sodium. A single lesion that is of no cosmetic significance may be treated with localized cryotherapy. Cutaneous leishmaniasis may respond to pentamidine isethionate. Alternate drugs include amphotericin B, ketoconazole, pentamidine, and allopurinol.

TOXOPLASMOSIS

Toxoplasmosis is covered in a separate chapter and will not be discussed (see Index).

NEMATHELMINTHES: NEMATODES (ROUNDWORMS)

Toxocariasis

Toxocara canis is the round worm of dogs. The normal life cycle of Toxocara canis includes the ingestion of the larval stages of the organism by an adult dog. The eggs contain first-stage larvae, whereas second-stage larvae are found in the intestinal wall and tissues of infected animals. Third-stage larvae can be found in the lung, and fourth-stage larvae can be found in the feces of infected hosts. Second-stage larvae penetrate the intestinal wall and enter the systemic circulation of the infected dog. The larvae may reach arterioles of various organs, causing localized granuloma. During pregnancy, the encapsulated larvae in the infected bitch are released and the larvae spread, reaching the liver of the fetus via the placenta. The newborn pups may also be infected by the larvae that are passed in the milk of the bitch. The larvae migrate to the lung of the pup, reaching the third stage when they are coughed, swallowed, and then passed to the small intestines, where they become fourth-stage larvae. They mature in the intestines in 3 weeks and begin to shed eggs in large numbers in the feces for the remainder of their lifetime. Man is an incidental host for Toxocara species.

Larvae cannot come to maturity, but once they reach the circulation, they can lead to forms of parasites of infection, either (1) systemic or visceral larva migrans, or (2) ocular larva migrans.⁴⁹ The systemic form of the disease occurs at age 2 to 3 years and in children with history of eating soil (pica). Children may develop cough, hepatosplenomegaly, lymphadenopathy, and eosinophilia⁵¹; ocular lesions in this form of the infection are rare.⁴⁹ Ocular larvae migrans occurs at age 3 to 40 years. Patients rarely have a history of pica, and there are no systemic manifestations, such as hepatosplenomegaly or lymphadenopathy. Patients with ocular larva migrans have no fever and have mild or absent eosinophilia. The Toxocara antibody titer is usually low or negative.

The diagnosis of toxocariasis is made by clinical findings of disease and by performing serologic testing. ELISA appears to be a sensitive serologic test and can be performed on ocular fluid specimens.

The treatment of visceral larva migrans includes the use of diethylcarbamazine, thiabendazole, and mebendazole. In cases of ocular larva migrans, steroids may be used to prevent inflammatory reactions after the death of the organism. Vitrectomy is helpful in the repair of retinal detachment, which may develop in cases of ocular toxocariasis. Laser photocoagulation has been used in a few cases with varying degree of success.

Ascariasis

Ascariasis is caused by the roundworm Ascaris lumbricoides. The disease is common, but ocular complications are rare. Ectopic migration of the adult worm may occur. Kaplan and associates⁵² reported on an intact adult Ascaris worm that was extracted from the lacrimal duct of an 18-month-old African girl. Roche⁵³ reported on a similar case in which an ectopic Ascaris worm was found in the lacrimal duct. Ascaris larvae do not develop in the eye, and larval granuloma do not occur.

Baylisascariasis

Baylisascariasis is caused by tissue invasion by the larvae of Baylisascaris procyonis, which are roundworms transmitted to humans by the raccoon. The adults of this young worm are long; males can measure 12 cm and females 23 cm. The larvae of this parasite are large and may reach 1000 to 2000 μm in length. They do little damage to their raccoon hosts, who become infected by eating the egg-containing larvae or a tissue of an intermediate host infected with the parasite, such as rodents and rabbits. Millions of eggs resembling Toxocara are shed daily and they can survive for many years. Humans are incidental hosts of this parasite and may acquire the disease by ingesting the eggs or drinking contaminated water. Children who keep raccoons as pets may be at risk. Ocular infection with the larvae of Baylisascaris procyonis may occur.

Onchocerciasis

Onchocerciasis is a disease caused by the nematode Onchocerca volvulus. The disease is known to afflict approximately 30 million people living in Africa and Central and South America. Humans are the only definitive host for O. volvulus. Other related species of Onchocerca may produce a similar disease in domesticated animals. Onchocerca cervicalis produces a disease in the horse similar to that found in man.⁵⁴ Furthermore, onchocerciasis has been produced in experimental animals. Onchocerca lienalis may produce onchocerciasis in the guinea pig under experimental conditions.⁵⁵ In humans, the adult worm of O. volvulus is found in the subcutaneous tissues, where it becomes coiled and gets encapsulated in fibrous tissues. Such tumors may contain adult worms and microfilariae. Microfilariae are present in skin nodules, subcutaneous tissue, and the skin. The adult worm gets encapsulated and enmeshed in a protective coating of the host's fibrous tissue, and the manner by which it derives its nutrition is not known. Most of the signs and symptoms of onchocerciasis are due to the presence of microfilariae in the tissues. The microfilariae may have a tendency to spread systemically and, in untreated patients, are found in the bloodstream. The main route into the eye, however, is from the skin of the face through the conjunctiva or cornea or by way of the bloodstream.⁵⁶ The microfilariae possess a certain enzyme activity that allows it to penetrate through collagenous connective tissue, such as the cornea.

The principal intermediate hosts of O. volvulus are many species of the black fly Simulium. Microfilariae are picked up from the skin by the black fly; the metamorphosis to an infective larva takes place in 6 to 10 days in the thoracic muscles. The mature larva migrates to the proboscis of the black fly, and when the infected black fly bites, the larva escapes to the skin of a new host and penetrates the wound. The larva grows in the host to become an adult worm in approximately 1 year. A heavily infected mother with microfilaria parasitemia may pass the disease to her fetus through direct transplacental microfilarial transmission. The possibility, however, has not been confirmed. It has been estimated that heavily infected patients may harbor between 50 and 200 million microfilariae in the skin at any one time. In Africa, the infection is common in regions of rapidly flowing small streams, where Simulium black flies breed. The prevalence of the disease decreases markedly beyond a distance of 5 miles from the stream. This is due to the fact that the distribution of the insect vector rarely goes beyond 2 to 3 miles from the water sources. In their daily biting cycle, female flies bite from dawn to dusk, usually outdoors and on the lower extremities.

Onchocerciasis is an unusual parasitic disease in humans. Because the most significant pathologic changes are due to the microfilarial stages of the parasite, the severe manifestations of the disease may take many years to develop. In many other parasitic infections due to nematodes, the parasite does not multiply in the body. Each microfilaria measures approximately 270 to 320 μm in length. The organism can be identified in tissue sections. Skin biopsy specimens of suspected areas help in establishing the diagnosis. The snip biopsy specimens of the skin can be examined for living microfilariae, either in water or in saline. The number of microfilariae can be expressed quantitatively.

In onchocerciasis, blinding lesions may affect the anterior and posterior segments, causing sclerosing keratitis, anterior uveitis, optic atrophy, and chorioretinopathy. The pathogenesis of chorioretinopathy remains to be elucidated. Several possible mechanisms have been suggested, including inflammatory reactions to dead microfilariae, eosinophil-derived toxic proteins, immune complex disease, secretory products from the microfilariae, and autoimmunity.^57–62 Many authors have supported the hypothesis that autoimmune reactions may play a role in the pathogenesis of chorioretinopathy in onchocerciasis. Recently, a recombinant antigen (designated Ov39) was isolated from an adult female O. volvulus cDNA library that demonstrated immunologic cross-reactivity with a 44-kilodalton component of the retinal pigment epithelium and other ocular tissues.^63,64 Cooper and associates^64a studied patients with onchocercal chorioretinopathy and determined whether they had enhanced lymphoproliferative response to Ov39 compared with those without chorioretinal disease. The lymphoproliferative responses to Ov39 were not found to be enhanced in patients with onchocercal chorioretinopathy. The role of Ov39-specific cellular autoreactivity in the pathogenesis of onchocercal chorioretinopathy could not be demonstrated, and the theory of molecular mimicry as a cause in the induction of autoimmunity could not be proved.

There are several laboratory tests to determine the diagnosis of onchocerciasis. The immunologic tests that are available include skin tests, gel diffusion tests, passive hemagglutination tests, complement fixation tests, immunofluorescent antibody tests, and ELISAs. The Mazzoti test is a useful aid in the diagnosis of onchocerciasis. This test consists of giving a small dose (50 mg) of diethylcarbamazine to an adult patient and then observing the development of the clinical reaction in the skin. The reaction consists of the development of discrete papular eruptions within 15 minutes after the ingestion of diethylcarbamazine.^65–67 The test is usually read at 3 hours and again at 24 hours.

Clinical studies have demonstrated the efficacy of ivermectin in onchocerciasis.^67,68 Ivermectin is given as a single oral dose of 150 μg/kg of body weight once or twice a year. It should not be given to children younger than 5 years of age or to those weighing less than 15 kg; to pregnant women; or to nursing mothers in the infant's first week of life.

Trichinosis

Trichinosis is a disease caused by Trichinella spiralis. The disease is common, though generally subclinical, and the infection affects certain areas of Central and North America and central Europe. The disease is perpetuated by the habit of eating undercooked pork. The larvae of Trichinella are produced by the adult worm in the gut wall, where they burrow in gaining access to the lymphatics and reaching the circulation. The larvae are carried to all parts of the body; they penetrate striated muscle with their spear-shaped apparatus and eventually become encysted and calcified. The orbicularis muscle is frequently affected, causing periorbital edema and conjunctivitis. In rare cases, papilledema and retinal hemorrhages may occur.

Loiasis

Loiasis is a parasitic infection in humans caused by the roundworm Loa loa. The adult worm is a threadlike, cylindrical parasite that has the ability to inhabit the ocular adnexa and the subconjunctival tissue. It may live in humans for up to 17 years, and the intermediate hosts and vectors are members of the Chrysops genus. The disease is restricted to Africa. Loa loa is called the eye worm, but it is primarily a cutaneous pathogen. The microfilariae are blood borne and may in rare cases invade the uveal tissue and the optic nerve, as well as many other organs in the body.

The parasite is known for its occasional presentation as an adult worm under the bulbar conjunctiva. Patients may complain of irritation and foreign-body sensation as the worm creeps in the periocular tissues. Temporary inflammatory reactions may cause swelling of the eyelid (Calabar swelling), which is a characteristic finding in patients with Loa loa infections. Loiasis causes vague symptoms of low-grade fever, myalgia, and paresthesia. The adult worm can migrate under the conjunctiva, and involvement of the eye causes irritation, hyperemia, periorbital swelling, congestion, pain, photophobia, and decreased vision.

Loiasis is diagnosed by detecting eosinophilia, and by demonstrating microfilariae in peripheral blood films taken during the day; microfilariae may be found in 20% to 30% of patients.

Treatment is accomplished by surgical removal of the adult filarial worms wherever accessible. The best time to remove the worms is when they appear under the conjunctiva. The use of cocaine or other local anesthetics may cause immobilization of the worm and allow surgical removal. Cryoprobe extraction may be successful in removing a subconjunctival Loa loa. Chemotherapy with diethylcarbamazine may also be effective.

The concomitant use of antihistamines or corticosteroids may be indicated in patients who have allergic reactions after the use of diethylcarbamazine. Prednisone may be given simultaneously with oral diethylcarbamazine. This proves to be efficacious in moderating the adverse reaction to diethylcarbamazine.

Wuchereriasis

Wuchereria bancrofti is another cause of systemic filariasis. The parasite rarely leads to ocular complications. Retinal involvement with hemorrhages have been reported.

Thelaziasis

Thelaziasis is a zoonotic eye infection that occurs in dogs, cattle, sheep, horses, deer, and other animals; it is caused by a nematode of the genus Thelazia. The eye worm has been reported in western North America and the Far East. The adult worms live and lay their eggs in the lacrimal ducts and conjunctival sacs of the host animals. The worms and/or hatched first-stage larvae are ingested by flies of the genera Musca and, less commonly, Fannia, as they feed on the host animal's eye secretions. The first-stage larvae migrate from the intestine of the fly to its ovarian follicles, where they molt twice and develop into the infective third-stage larvae, eventually working their way into the proboscis of the fly. When the fly feeds on the eye secretions of an uninfected animal, the infective larvae are released into the lacrimal fluid, where they molt into fourth-stage larvae. They then migrate to the lacrimal ducts, where they develop to adulthood. Humans rarely serve as incidental hosts. Human thelaziasis is caused by Thelazia californiensis in the United States^69–71; Thelazia callipaeda (also known as Filaria lacrimalis) in India,⁷² Bangladesh,⁷³ Korea,⁷⁴ Indonesia,⁷⁵ Japan,⁷⁶ Thailand,⁷⁷ China,^78,79 and Russia⁸⁰; and Habronema in Australia.⁸¹ The threadlike eye worms have a creamy-white cuticular covering with closely packed transverse striations.⁷⁴ Females measure up to 1.7 cm in length; males are somewhat smaller. In reported cases of thelaziasis in humans, the worms are usually located in the conjunctival cul-de-sac, but rarely in the anterior chamber.⁷³

Diagnosis of thelaziasis is based on observation of the worms, and their identification after removal. Treatment consists of removing the surface worms with forceps under topical anesthesia. Worms located more deeply are removed surgically.⁸¹ Small worms may be missed initially, and may cause recurrence of symptoms as they grow. Ivermectin has been used successfully in the treatment of thelaziasis in cattle.⁸²

Dirofilariasis

Dirofilariasis is a zoonotic disease among raccoons, dogs, and cats, which is accidentally transmitted to humans presumably by the same vector arthropods that infect their usual animal hosts, namely Culex and Aedes mosquitoes. Filariid worms of the genus Dirofilaria are the causative agents of this disease, of which three species have been identified in humans: Dirofilaria tennius, parasitic in raccoons, which is the most common species acquired in North America; Dirofilaria immitis, the heartworm of dogs; and Dirofilaria repens, which is normally found in the subcutaneous tissues of cats and dogs in Asia, Europe, and South America.

Dirofilaria conjunctivae, so named because of the tendency of the parasite to locate near the eye, does not show any significant taxonomic differences from Dirofilaria repens.^83,84 Taxonomic identification of worms belonging to the genus Dirofilaria is based on cuticular morphology,⁸⁵ anatomic location, and geographic considerations.

Humans are a suboptimal host: that is, the parasite dies before producing microfilariae. Immature worms, unmated adult worms, and sexually mature worms containing microfilariae have been detected in humans, but microfilariae have never been found in human blood. The female worm is approximately 155 mm long and the male approximately 85 mm long. Most reports show a well-encapsulated, nonviable parasite in subcutaneous nodules or in cardiopulmonary “coin” lesions and infarcts. For reasons that are unclear, infection in children is rare. The ocular form of dirofilariasis in man is cosmopolitan, with cases reported sporadically from Australia,⁸⁶ Asia,^87–91 Europe,^92–94 Africa,⁹⁵ and the Americas.^96–98 In reviewing the cases of dirofilarial ophthalmic infections in various parts of the world, it is apparent that common sites of involvement, listed from most to least common, are the subcutaneous tissues of the eyelids and periorbital region,^{94,96,97,99–109} conjunctiva,^{87,93,95,102–117} orbit,^{88,93,94,106,118–120} vitreous,^121–125 anterior chamber,^86,98,126 and sclera. Presenting symptoms include eye irritation, ocular pain, itching and redness, and diplopia. Detection of the viable parasite itself is perhaps the clearest indication of dirofilariasis, although it is more common to find a well-encapsulated, nonviable parasite causing orbital proptosis and symptoms of an orbital tumor. Diagnosis is based on serologic testing. A fluorescent antibody test is used that can differentiate Dirofilaria from Toxocara and Ascaris infections, and a recently developed diagnostic ELISA technique is highly specific.¹²⁷

Local excision of the mass of encapsulated parasites or surgical removal of the viable worms is adequate treatment. If secondary infection of the orbit is suspected, treatment with intravenous penicillin and/or corticosteroids is advisable.

Dracunculiasis

Dracunculiasis, also known as dracunculosis or dracontiasis, is caused by the presence of the guinea worm Dracunculus medinensis in the deep connective and subcutaneous tissues of humans. The adult worms are elongated nematodes. The females can measure up to 120 cm in length and approximately 2 mm in diameter; however, the male is less than 4 cm in length. The gravid female, whose body is almost completely filled by its larvae-distended uterus, approaches the human skin surface, usually in the distal portions of the lower extremities. The adult worms provoke the formation of burning blisters that finally ulcerate. If the affected part comes in contact with water, a loop of the worm's uterus prolapses through its body wall and ruptures, liberating large numbers of first-stage larvae. These are ingested by copepods of the genera Cyclops, Mesocyclops, Tropocyclops, and Thermocyclops, in which they undergo two molts to reach the infective third-stage larvae. If these copepods are swallowed in drinking water, the contained infective larvae are released and migrate to subcutaneous tissue, where they undergo two further molts before maturation. After mating, the male worms die and become encysted, while the fertilized females move to the extremities and emerge through the skin about a year after infection.

Dracunculiasis is highly endemic in poverty-stricken areas, particularly rural communities lacking any form of public drinking water supply. It tends to be seen in India, western and central Africa, and southwestern Asia.

A few cases^128–130 of ocular dracunculiasis have been reported in the literature over the past five decades. In these cases, the worms were found behind the orbital septum¹²⁸ in the subconjunctival space,¹²⁹ in an intraocular abscess, and in a cystic mass of the upper lid.¹³⁰ Retrobulbar invasion results in proptosis and loss of the eye, whereas more superficial involvement causes intense edema of the soft tissue of the eyelid and conjunctiva. Diagnosis is based on demonstration of the Dracunculus female in surgical specimens.

Treatment consists of surgical removal of the worms. Supportive drug treatment includes oral administration of niridazole, thiabendazole, metronidazole,¹³¹ and mebendazole.¹³²

PLATYHELMINTHES: CESTODES (TAPEWORMS)

Echinococcosis

Echinococcosis is caused by Echinococcus granulosus. The adult worm lives in the intestines of dogs and humans, who are intermediate hosts for the parasite (Fig. 1). The adult worm is small, measuring 2.5 to 9 mm in length. It does not harm the canine host. When eggs are ingested by humans, they liberate larvae that may reach the tissues and undergo central vesiculation, forming a cyst. Intraocular hydatid cysts are rare but have been reported. More commonly, orbital hydatid cysts may cause proptosis and restriction of ocular movements.^133,134

Cysticercosis

Cysticercosis is a common cause of serious morbidity in Mexico and Central American countries. It is caused by the eggs of the adult pork tapeworm Taenia solium, which are either ingested or released by reverse peristalsis in cases of intestinal obstruction (Fig. 2A and B). Eggs mature, and the larvae penetrate the intestinal mucosa, reaching the retinal circulation. The larva of Taenia solium (Cysticercus cellulosae) is the most common tapeworm that invades the human eye. The larvae (cysticerci) may cause localized abscesses of the eyelids^135–137 and conjunctiva.¹³⁸ A subconjunctival abscess may form secondary to the larva of Taenia solium (Cysticercus).¹³⁹

The Cysticercus larvae may reach the eye by way of the choroidal circulation and gain access to the subretinal space.¹⁴⁰ The larvae may migrate under the retina and can live in the eye for years. Persistence of the larvae within the ocular tissue may stimulate chronic inflammatory reactions and fibrosis.¹⁴¹ In rare instances, the larvae may be seen in the anterior chamber. In the subretinal location, the parasite may stay in the eye for a while, but with increasing fluid accumulation in the bladder of the Cysticercus, the retina may become detached. The Cysticercus may gain free access to the vitreous cavity and occasionally may cross through the pupillary opening and appear in the anterior chamber. Death of the larvae within the ocular tissues can stimulate a severe inflammatory reaction.

Cysticercus larvae may be removed from the subretinal location by surgical intervention without permanent damage to the eye. Once the Cysticercus reaches the vitreous, the prognosis is worse and its removal more difficult. If the parasite dies within the vitreous cavity, its toxic cyst fluid is released, leading to a severe inflammatory reaction. Subretinal Cysticercus can be treated with photocoagulation in an attempt to kill the organism and provide a firm scar. Pretreating such patients with systemic corticosteroids is mandatory to minimize the inflammatory reaction. The ocular adnexa, including the conjunctiva and extraocular muscles, may be involved by the Cysticercus.

The most serious form of the disease is cysticercosis of the brain, which leads to seizures and sometimes paralysis and death. The central nervous system lesions seem to resolve spontaneously and may relentlessly cause hydrocephalus and death. Death of larvae within the brain can lead to localized inflammation, fibrosis, and calcification. If the larvae are in the Aqueduct of Sylvius, it can cause hydrocephalus. The severity of the disease depends strictly on the number of eggs ingested. Radiography on the subcutaneous tissue may reveal calcification at the sites of the Cysticercus larvae.

Coenuriasis

Coenuriasis, a tapeworm disease also known as coenurosis, is caused by Coenurus cerebralis, the larval cystic form of the taeniid worms Multiceps multiceps and Taenia bremneri. The parasite affects primarily the central nervous system of sheep, causing the syndrome of “blind staggers.” In humans, who are an unusual incidental host, Coenurus bladder worms have been reported in the central nervous system and occasionally in the eye and subcutaneous tissues, particularly in Africa.

In intraocular cases, it is commonly found in the subretinal space and vitreous,¹⁴² and rarely in the anterior chamber. In superficial infestations, however, it is mostly located in the subconjunctival space and less commonly elsewhere.⁴⁹ It is believed that subconjunctival and subcutaneous infestation, which occurs mostly in children, results from inoculation of the larva directly into the skin or through the conjunctiva during early toddler life, when the skin and eyes are frequently close to ground that may be contaminated.

Sparganosis

Sparganosis is infection with spargana (plerocercoid larvae) of various species of the diphyllobothriid tapeworm Spirometra, which cannot grow to adult worms in humans, but can reach maturity in certain animals, such as cats and dogs.⁴⁹

It has been shown that eggs of Spirometra hatch in water, and the emerging coracidia are ingested by copepods of the genus Cyclops, where they develop into procercoid larvae.⁴⁹ When infected copepods are swallowed by cats or dogs, the procercoids transform into plerocercoid larvae and develop into adult worms. Humans, frogs, snakes, and some birds are acceptable paratenic hosts, although infection remains at the plerocercoid level.

Sparganosis may be transmitted in one of the following ways: (1) by drinking water contaminated with copepods harboring the infective procercoids; (2) by ingesting the raw flesh of frogs, snakes, or birds containing the infective plerocercoids; or (3) by poulticing open wounds with the flesh of infected frogs or snakes, a recognized practice in the Far East.

Presenting symptoms of ocular sparganosis are nodule formation, lacrimation, edema, redness and pain, and in the case of retrobulbar invasion, a bulging orbit with corneal ulceration. A presumptive preoperative diagnosis may be made on demonstration of periocular nodules.

PLATYHELMINTHES: TREMATODES (FLUKES)

Schistosomiasis

Schistosomiasis is a disease caused by Schistosoma haematobium, Schistosoma mansoni, and Schistosoma japonicum. The life cycle of S. haematobium is shown in Figure 3. Although the adult worms of Schistosoma live in the intravascular space, the eggs of S. haematobium are found in urine of humans, and the eggs of S. mansoni and S. japonicum are found in feces of humans. The eggs of Schistosoma are liberated from the tissues into the lumen of the bladder or the intestine, and the miracidium is liberated from the eggs. The miracidium escapes when a person urinates or defecates in water; the miracidium then swims in the water searching for the appropriate snail to penetrate; it then undergoes a cycle of development, giving rise to cercariae, which are infective to humans. Humans acquire the infection by exposure to water into which the snails have liberated cercariae. The cercariae have certain organs that allow them to penetrate the skin of humans and invade the circulatory system.

Intraocular infection by Schistosoma is extremely rare. Occlusion of the central retinal artery has been reported to be caused by the egg of S. mansoni. Occasionally, eggs may be discharged into the circulation, and embolization of the eggs may lead to development of a granuloma in the ocular adnexa. The conjunctiva may be the site of the localized granuloma owing to embolization of the eggs of S. haematobium.^143,144 In rare instances, the granuloma may be found in the lacrimal gland.¹⁴⁵

Paragonimiasis

Paragonimiasis is primarily a lung infection and is often referred to as pulmonary distomiasis. It is caused by trematodes of the genus Paragonimus, particularly the Oriental lung fluke Paragonimus westermani in humans. The adult worms are reddish brown, plump, ovoid flukes measuring up to 16 mm in length and 8 mm in width. They encyst in the lungs, and the eggs discharged in the bronchioles are either expectorated with sputum or swallowed and subsequently passed in feces.¹ Eggs hatch in water after 3 to 4 weeks, and the miracidia invade snails belonging to several families, mainly Thiaridae, Pleuroceridae and Hydrobilidae.^1,2 In 3 to 5 months, successive generations of mother sporocysts, rediae, daughter rediae, and finally cercariae are produced in snails. The cercariae then leave the snails and penetrate freshwater crabs and crayfish, where they encyst in the gills, muscles, legs, and viscera, developing into the infective metacercariae in 6 to 8 weeks. Humans acquire the infection by eating raw or undercooked crab or crayfish containing the infective metacercariae.

Paragonimiasis in humans is largely restricted to the Far East, where dietary habits (consumption of raw fish) favor infection by Paragonimus westermani. Furthermore, most of the flukes migrate to the lungs. Consequently, extrapulmonary paragonimiasis is rarely seen in humans, especially outside the Far East.

Ocular symptoms of the disease result from cerebral infection, or, much less commonly, relate to an existing worm invasion of the subconjunctival space, eyelid, or orbital tissue.^146–148 In cases of cerebral paragonimiasis, the main ophthalmologic signs include homonymous hemianopia, papilledema, impaired visual acuity, and optic atrophy. The clinical features of intraocular paragonimiasis include repeated attacks of severe intraocular pain that is not alleviated by analgesics. Anterior uveitis and spontaneous hyphema develop, along with profound visual loss and secondary glaucoma.

In most cases, a diagnosis of paragonimiasis can be made after demonstration of the characteristic eggs in aspirated pleural effusion, or in the sputum or feces. Pulmonary involvement can be demonstrated by x-ray of the chest. Serologic tests are used for diagnosis of extrapulmonary paragonimiasis. Complement fixation test, countercurrent electrophoresis, and ELISA are found to be highly sensitive and specific.¹⁴⁹ An intradermal test is available for screening in epidemiologic surveys.

Ocular paragonimiasis is treated by surgical removal of the worm. When the parasite invades the vitreous, vitrectomy should be performed. The use of systemic praziquantel or niclofolan is recommended.

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