Helminth Infections

Clinical Features

Human infection with adult T. solium is usually asymptomatic but may be associated with minor gastrointestinal symptoms. Tissue infections with the metacestode larvae of T. solium (cysticercosis) may involve many parts of the body but rarely cause serious disease except when there is cardiac or central nervous system (CNS) involvement. Patients may harbor both adult worms and cysticerci, which can arise from autoinfection. Cysticercosis of the CNS (neurocysticercosis) is the most common cause of acquired epilepsy in endemic areas (e.g., Mexico, South and Central America, the Philippines, and Southeast Asia) and possibly the most common cause of epilepsy in the world. Neurocysticercosis affects males and females equally and has a peak occurrence in young adults 25 to 35 years old, although infection probably peaks at an earlier age (5 to 15 years). Cysts generally become symptomatic when they begin to die and elicit an inflammatory host response. Clinical manifestations of neurocysticercosis vary depending on the location of the cysts. In addition to seizures, headache and mass effects due to intracerebral lesions, hydrocephalus, chronic meningitis, and compression of the spinal cord have been associated with cysts in intraventricular, subarachnoid, and spinal cord locations, respectively. Fever is not a common feature of neurocysticercosis.

Pathologic Features

Microscopic Findings

Taenia solium and T. saginata proglottids are usually viable when passed in the feces, and when processed by the laboratory into histologic sections they are readily identifiable by their morphologic features. The proglottids of these two species are similar and the eggs are virtually identical. It is difficult to separate these two species based on the number of uterine branches in histologic sections. Taenia species proglottids can be identified by their microvilli-lined tegument, smooth muscle, and calcareous corpuscles in a loose parenchyma ( Figure 27-1 ). Taenia species eggs in histologic sections are 30 to 35 μm in diameter and have a thick radially striated shell ( Figure 27-2 ). Taenia species gravid proglottids can be distinguished from those of Dipylidium caninum, the dog tapeworm that occasionally infects children, because the eggs of the latter occur in packets ( Figure 27-3 ).

Taenia solium cysticerci are fluid-filled cysts with a single invaginated protoscolex. The tegument and bladder wall are morphologically similar to those of proglottids except thinner. Viable cysticerci sectioned through a plane that demonstrates the invaginated neck region or protoscolex are easily recognizable ( Figure 27-4 ). The diagnosis can be difficult if the histologic section contains only a fragment of the cyst wall and no neck region or protoscolex. Occasionally an aberrant form of cysticercus (cysticercus racemosus) develops in humans with a predilection for the base of the brain and subarachnoid space. Cysticercus racemosus produces no protoscolices, but the bladder wall proliferates extensively forming irregular masses resulting in a pattern resembling a compact cluster of grapes. Viable cysticerci may compress surrounding structures but usually cause minor host response. In contrast, dying or dead cysticerci provoke an intense inflammatory exudate comprised of neutrophils, eosinophils, histiocytes, and fibrin. Eventually, the lesion develops into granulomatous inflammation with formation of epithelioid cells and giant cells. The terminal event is fibrosis and calcification. A presumptive diagnosis of cysticercosis may be rendered upon finding only calcareous bodies (10- to 20- μm diameter laminated rings), providing all other known circumstances are supportive. Coenuri, the metacestode larvae of Taenia multiceps and T. serialis, have similar morphologic features to cysticerci but can be distinguished by the presence of multiple invaginated protoscolices ( Figure 27-5 ).

Ancillary Studies

The most practical approach to the diagnosis of adult T. solium infection is the examination of feces for eggs or proglottids. Samples taken on several successive days may be needed, and concentration techniques may improve sensitivity. Care must be taken to avoid ingestion of eggs because they are infective.

Neurocysticercosis may be suspected based on imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]). Examination of cerebrospinal fluid (CSF) may reveal lymphocytic or eosinophilic pleocytosis, low glucose, and high protein levels.

Serology is available commercially or through the Centers for Disease Control and Prevention (CDC), which indicates prior exposure to T. solium , but cross- reactivity may occur with other cestode antigens. Negative serology does not exclude the diagnosis in the presence of characteristic CT and MRI results. Immunoblotting with the purified glycoprotein fraction of the cyst fluid may be a more sensitive and specific method.

Differential Diagnosis

The differential diagnosis of adult T. solium taeniasis includes other tapeworms particularly T. saginata . DNA probes can reportedly differentiate the two species, if this has not been possible from examination of proglottids or eggs. The differential diagnosis of neurocysticercosis is broad due to the number of different CNS sites that may be involved and the inflammatory response of the host.

Gliomas, cavernous malformations, and echinococcal cysts are differential diagnostic considerations for subarachnoid neurocysticercosis. Carcinomatous meningitis and granulomatous meningitis (sarcoidosis and mycobacterial, fungal, and syphilitic meningitis) are considerations when there is chronic basal arachnoiditis. Choroid plexus cysts, ependymal cysts, and colloid cysts are considerations for intraventricular neurocysticercosis.

The differential diagnosis of other cystic CNS lesions of parasitic, congenital, or traumatic origin may be considerations. Neurocysticercosis should also be considered in patients with brain infarction who are younger than 40 years old, are from endemic areas, and lack a predisposing factor.

Prognosis and Therapy

Niclosamide and praziquantel are two oral medications that are effective in treating adult T. solium intestinal infections. Some authors suggest using a mild laxative 1 to 2 hours after niclosamide treatment to avoid the possibility of internal autoinfection. Additional considerations apply during pregnancy.

Neurocysticercosis is not a single disease entity, and treatment depends on a variety of clinical factors. Medical treatments include antiepileptic drugs, cysticidal agents (i.e., albendazole and praziquantel), and anti-inflammatory medications. Surgery may be necessary (e.g., for shunt placement), but earlier diagnosis has made it more likely that pharmacologic treatment alone will be sufficient.

The prognosis for adult T. solium intestinal infections is good, but that for neurocysticercosis is variable depending on the location of lesions, the inflammatory response, and associated complications. A conservative estimate is that worldwide 50,000 deaths occur each year due to neurocysticercosis.

SPIROMETRA SPECIES (SPARGANOSIS)

Sparganosis is caused by at least four species of Spirometra larvae, pseudophyllidean tapeworms. Sparganosis is most common in Southeast Asia but can be acquired in the United States. Dogs and cats, among other animals, serve as definitive hosts, whereas humans serve as second intermediate and paratenic hosts. Humans can become infected with spargana in three ways: (1) drinking water contaminated with infected Cyclops (procercoid larva), (2) consuming a sparganum (plerocercoid larva) in improperly cooked flesh of a second intermediate or paratenic host (amphibian, reptile, bird, mammal), or (3) applying poultices of an infected second intermediate or paratenic host to an open wound.

An extremely rare form of sparganosis, not completely understood but thought by some to be caused by Spirometra (Sparganum) proliferum, occurs when the sparganum begins uncontrolled proliferation by branching and budding. Lesions usually begin as subcutaneous nodules, but the proliferating sparganum can disseminate to any part of the body seeding the tissues with thousands of variously sized spargana.

Clinical Features

Up until 1996, 62 cases of sparganosis had been reported in the United States mainly from the Southeast. Spirometra mansonoides is the species most frequently encountered in U.S. Gulf States. Japan and Korea reportedly have the highest prevalence of sparganosis, mainly due to diet-associated infections. Ingestion of contaminated water is the most common source of infection in the Western Hemisphere. Imported cases from Southeast Asia may have been acquired as long as 19 years prior to diagnosis. Most commonly sparganosis presents as a slow-growing subcutaneous mass that may be migratory. Multiple other sites of involvement have been reported, including the breast, lung, abdominal cavity, genitourinary tract, and heart. The most serious infections involve the eyes and CNS. Infections in the CNS can present in a variety of ways depending on the size and location of the lesion, but seizures, headache, and hemiparesis are commonly reported. Vasculitis with stroke has also been reported. Ocular involvement can lead to blindness.

Pathologic Features

Microscopic Findings

Spargana are elongate, flat, solid-bodied larvae that may appear spherical in histopathologic sections. The living tegument is lined with microvilli, allowing for the absorption of nutrients. The parenchyma is a loose stroma containing smooth muscle cells, branching excretory channels, and calcareous corpuscles ( Figure 27-6 ). They have no reproductive organs. Apparently viable spargana can cause an inflammatory response including abscess formation, chronic inflammation, and tissue eosinophilia. As the worm disintegrates, it provokes granuloma formation with palisading epithelioid cells and giant cells. Eventually the worm is completely destroyed and what remains is a tortuous tract with central caseation necrosis.

Ancillary Studies

There may be eosinophilia in blood samples that can be pronounced. Peripheral eosinophilia is common in CNS infections, but curiously cerebrospinal fluid (CSF) eosinophilia is not a reported feature.

Imaging studies, of CNS lesions, especially CT and MRI, can be quite characteristic. In particular there may be a tunnel sign in postcontrast MRIs. Punctate calcifications, “calcospherules,” within the parasite are better seen by CT. Repeat imaging has been recommended to identify changes in the size and location of lesions to indicate that the organism is still alive and that its surgical removal is indicated.

Enzyme-linked immunosorbent assay (ELISA) of serum or CSF for sparganosis-specific antibody is sensitive and specific. Identification of the organism in histopathologic specimens provides definitive diagnosis but may not always be surgically possible. A preoperative diagnosis of cerebral sparganosis could reportedly be established based on clinical data, positive ELISA results, and characteristic imaging findings.

Differential Diagnosis

The differential diagnosis of cutaneous sparganosis includes other parasitic diseases that can present as migrating subcutaneous masses, including gnathostomiasis, paragonimiasis, loiasis, and dracunculiasis. A longstanding lesion that becomes calcified may clinically mimic varicose veins. Other inflammatory and neoplastic conditions may enter the differential diagnosis.

Cerebral sparganosis has a differential diagnosis that includes primary and metastatic brain tumors and other inflammatory granulomatous processes.

Prognosis and Therapy

The prognosis is good for subcutaneous and intramuscular nonproliferative sparganosis if the organism is removed surgically. Ocular and CNS lesions can have significant sequelae including hemiparesis and blindness.

Antiparasitic treatment (praziquantel) has reportedly had limited success in treating peripheral sparganosis and no effect on spargana in the CNS. Surgical excision of the organism in the CNS may therefore give the best response.

Human proliferative sparganosis caused by S. proliferum, a type of sparganum that buds and branches and that may become widely disseminated, may result in death, as attempts at surgical removal are usually unsuccessful. The usual species seen in sparganosis acquired in the United States, Spirometra mansonoides, is nonproliferating.

ECHINOCOCCUS SPECIES, LARVA (HYDATIDOSIS)

Echinococcosis more accurately refers to infections caused by adult tapeworms in the definitive host, which humans are not. Hydatidosis and hydatid disease are more appropriate terms and refer to infection by the Echinococcus larva (metacestode). At least four species of Echinococcus larvae cause disease in humans. Echinococcus multilocularis causes alveolar hydatid disease, is focally distributed throughout the world, and is the second most common echinococcal larval tapeworm infecting humans. Echinococcus vogeli causes polycystic hydatid disease and prevails in Central and South America. Echinococcus oligarthus also causes polycystic hydatid disease and occurs in Central and South America. Echinococcus granulosus causes cystic hydatid disease and is the most common cause of hydatid disease. Therefore, the following discussion is limited to E. granulosus infections.

Echinococcus granulosus has a worldwide distribution but is a more serious problem in sheep- and cattle-raising regions. Dogs are the most common definitive hosts, but many other animals are also infected including wolves, foxes, and cats. The adult tapeworm is minute, consisting of a piriform scolex with armed rostellum and four suckers followed usually by only three proglottids. Echinococcus granulosus eggs are morphologically indistinguishable from most Taenia species eggs. A variety of animals serve as intermediate hosts, including sheep, cattle, pigs, and horses. Humans are usually an accidental dead-end host. Intermediate hosts acquire their infections by ingesting infective eggs that eventually develop into larval hydatid cysts. Hydatid cysts can develop anywhere in the human body, but the liver is the most common site. The definitive host becomes infected by feeding on the viscera of animals contaminated with hydatid cysts. Hydatid cysts in human liver grow slowly, about 1 mm in diameter per month.

Clinical Features

The initial stage of infection following oral ingestion of E. granulosus eggs is asymptomatic, and the infection may remain so for years or even for life. The development of morbidity is related to several factors including the number, size, site and stage of cyst development, host reaction, and pressure effects of cysts on adjacent tissues. The average diameter of asymptomatic cysts is reportedly about 4 cm, whereas symptomatic cysts average about 10 cm in diameter. Hydatid cysts affect both genders equally over a wide age range. Most hospitalized patients are 21 to 40 years old, and morbidity may peak in 6- to 20-year-old individuals. A single cyst in one organ is present in 40% to 80% of patients with primary cystic echinococcosis. The liver is most frequently involved, followed by the lung, kidney, and spleen, although any organ may be involved including the heart and the CNS. Clinical presentations vary and include abdominal pain, hepatomegaly, cholestasis, biliary cirrhosis, portal hypertension and ascites for liver cysts, and cough, dyspnea, hemoptysis, and pleuritis for lung cysts. In both organs, erosion of cysts into the biliary or bronchial trees can cause obstruction and postobstructive bacterial infections. Cysts can also become infected and form bacterial abscesses. Ruptured cysts may cause severe allergic reactions including anaphylaxis, and they may also lead to the seeding of daughter cysts to other organs, increasing morbidity and mortality.

Pathologic Features

Microscopic Findings

The hydatid cyst wall is composed of two layers: an outer laminated membrane and an inner germinal membrane ( Figure 27-7 ). The laminated membrane is approximately 1-mm thick, and its layering is made more pronounced by use of the Gomori methenamine-silver (GMS) stain ( Figure 27-28 , presented later in the chapter). The germinal membrane is 20 to 25 μm thick and contains nuclei and calcareous corpuscles. In fertile cysts, brood capsules and individual protoscolices arise from the germinal membrane (see Figure 27-7 ). A fertile cyst may contain thousands of brood capsules, and each brood capsule may house a dozen or more protoscolices. Daughter cysts usually form within the primary cyst from the germinal layer, brood capsules, or protoscolices. Brood capsules, protoscolices, hooklets, fragments of germinal membrane, and daughter cysts may be found floating in the cyst fluid. Daughter cysts are morphologically identical to the parent cyst and may have escaped from a damaged parent cyst, developing into exogenous daughter cysts. Some cysts are sterile in that they form no protoscolices, brood capsules, or daughter cysts.

Hydatid cysts grow slowly, taking several years to develop, a time when the patient is usually asymptomatic. During this period the cyst provokes an inflammatory reaction that eventually results in the cyst being surrounded by a thick fibrous capsule. Viable, nonruptured, primary cysts cause damage resulting from compression of adjacent tissues. Dead or ruptured cysts pose serious problems and complications. Fragments of necrotic laminated membrane can cause an acute inflammatory reaction with tissue eosinophilia, granuloma formation with giant cells, and broad areas of necrosis. Dying protoscolices eventually calcify. Sometimes only the birefringent, acid-fast hooklets are preserved in areas of necrosis. Secondary bacterial infection and suppuration may accompany disintegration of cysts.

Ancillary Studies

Radiologic findings (ultrasound, CT, and MRI) can suggest the diagnosis of hydatid cyst. ELISA and Western blot serology (available through the CDC in the United States) can confirm the diagnosis. The sensitivity of serology for liver cysts is higher than that for lung cysts, but a proportion of patients with hydatid cysts in either site do not produce detectable specific serum antibodies. As imaging studies are more sensitive than serology, characteristic imaging studies can still suggest the diagnosis of hydatid cyst even in the presence of negative serology.

Differential Diagnosis

Abscesses, neoplasms, and other conditions may enter the differential diagnosis of hydatid cysts of the liver. A variety of other conditions may be differential diagnostic considerations in other sites.

Prognosis and Therapy

There are several therapeutic approaches for the treatment of cystic hydatid disease. Surgery can be successful, especially when there are low numbers of cysts and there is limited organ involvement not relating to vital locations. Puncture-aspiration-injection-reaspiration (PAIR) is a less invasive technique involving injection of parasiticidal fluids into a cyst, but this approach has limitations, including being contraindicated in lung, heart, and CNS cysts, and in liver cysts communicating with the biliary tree due to the risk of chemical cholangitis. A new technique for which there are few published data is percutaneous thermal ablation. Drug treatment with albendazole or mebendazole is indicated for inoperable cysts, and it has provided improvement in a majority of patients but cure in a minority. Albendazole is better absorbed from the gastrointestinal tract and is the favored medication. The size and location of cysts can also influence the likelihood of success with drug treatment. For example, bone cysts reportedly respond less well than cysts at other sites. Serial imaging may be used to monitor therapy. Surgery can be curative, as can drug therapy in a minority of cases (10% to 30%). Drug therapy has a beneficial effect on cysts in most cases (50% to 70%), but 20% to 30% of patients do not show evidence of improvement. Relapses can also occur after drug therapy, which can usually be retreated.

Clinical Features

Schistosomiasis may present as a dermatitis (schistosome dermatitis or cercarial dermatitis) associated with skin penetration by cercariae, acute schistosomiasis (Katayama fever), or chronic schistosomiasis. Schistosome dermatitis is caused by skin penetration by cercariae, and it initially presents with a prickling sensation followed by a macular rash several hours later. In previously sensitized individuals it may develop into a pruritic maculopapular rash lasting several days.

Acute schistosomiasis (Katayama fever) occurs in previously uninfected individuals 2 to 8 weeks after infection with S. japonicum and S. mansoni in particular. There is an acute onset of fever, chills, headache, myalgia, abdominal pain, diarrhea, and occasionally bloody stools. A majority of patients also develop respiratory symptoms and interstitial infiltrates in chest radiographs. Hepatosplenomegaly and lymphadenopathy are common, and eosinophilia is usually present. Eggs may not, however, be detected in feces until later in the course of disease. The illness usually resolves in a few weeks, but the course may be complicated by lesions at the sites of ectopic egg deposition such as the CNS. Heavy infection may result in death.

In chronic schistosomiasis with light or moderate infections, symptoms may be mild or absent, but there is often eosinophilia. Moderate to heavy infections can lead to morbidity associated with anemia and malnutrition, particularly in children and pregnant women. Patients with heavy S. mansoni infection can present with fatigue and abdominal pain with intermittent diarrhea or dysentery. Intestinal strictures and large inflammatory masses may mimic neoplasms. Some patients present with hepatomegaly, and after years of infection about 5% to 10% develop periportal fibrosis (Symmers’ “pipestem” fibrosis). Portal hypertension may develop, leading to esophageal varices. Coexisting liver disease such as alcoholic cirrhosis and chronic hepatitis B and C may lead to jaundice and ascites. Patients with hepatitis B and S. mansoni infections have a higher risk for the development of hepatoma than patients with hepatitis B infection alone.

Eggs may cause pulmonary lesions by traveling through portosystemic collateral vessels, bypassing the liver. These can cause granulomatous pulmonary arteritis that can progress to cor pulmonale. The CNS is rarely involved by S. mansoni (usually spinal cord or cauda equina) and even less commonly by S. haematobium , but it may be involved in up to 5% of S. japonicum infections.