The Eosinophilic Patient with Suspected Parasitic Infection

Clinical Features

Eosinophilia in a traveler returning from long-term residence or visit to the developing world or in an immigrant or refugee from a tropical area should first suggest the possible presence of a helminthic infection. Although eosinophilia particularly suggests presence of a helminth, the absence of eosinophilia cannot exclude these parasites. With a few notable exceptions, protozoan and other infections are seldom associated with eosinophilia, and as noted above, non-infectious etiologies must always be considered.

Eosinophil counts are generally higher in the early acute invasive phase than in chronic helminthic infections, particularly during initial infection with the parasite in a non-immune individual, and there may be considerable variation in the person-to-person response to the same helminth. Eosinophilia in the presence of a helminthic infection may be considered to be an adaptive increase in the number of eosinophilic cells available to damage the parasite. In addition, eosinophilia under these circumstances may be associated with qualitative changes in the eosinophils themselves.

The greatest number of tissue and blood eosinophils are found in infections in which the association of the parasite with host tissue is closest, that is, those with migrating larvae or extended retention of parasite lifecycle stages in tissue. Especially high eosinophil levels may be found in Ascaris pneumonia, strongyloidiasis, filariasis, tropical pulmonary eosinophilia, and acute schistosomiasis. Another situation leading to high eosinophilia is when humans become accidentally infected with parasites whose definitive host (host in which sexual maturity and reproduction of the parasite takes place) is in another animal species. The “lost” larval stages wander in the tissues until they die or become encysted; examples of such infections are trichinosis and visceral larva migrans (toxocariasis caused by dog and cat roundworm species). Intestinal helminths that remain in the bowel lumen and do not invade the intestinal mucosa (e.g., adult Ascaris and tapeworms) cause minor or no eosinophilia. Increased eosinophilia can develop after drug treatment of helminths, and it may take several months for elevated eosinophil levels to return to normal after initial parasite destruction.

Diagnosis

The diagnosis of common intestinal helminths is usually made by finding the characteristic egg or larva in stool specimens submitted for microscopic examination. Clinical recognition and diagnosis of extraintestinal or disseminated parasites may be more difficult. If the stool examinations do not suggest a likely diagnosis, the following approach is suggested in the work-up of the patient with suspected parasite infection.

• 1.

  The geographic or travel history of the patient with eosinophilia may indicate a past exposure to parasites. Because the patient with tissue-stage parasites can have either multiple systemic symptoms or few clinical symptoms to report, and often will have negative stool examinations for ova and parasites, the geographic history is of prime importance. For instance, the history of swimming in freshwater lakes or rivers in endemic areas of Africa, South America, or Asia should suggest the possibility of schistosomiasis.

• 2.

  In the immunocompromised patient with fever, pneumonia, or central nervous system (CNS) signs, Strongyloides should be considered even in the absence of eosinophilia.

• 3.

  The history of exposure to pets, livestock, and wild animals or mosquito bites in rural areas may provide valuable clues to potential parasite exposure (e.g., filariasis, toxocariasis, cutaneous larva migrans, echinococcosis).

• 4.

  The history of eating exotic or raw, smoked, pickled, or undercooked food may provide additional clues to past opportunities for parasite exposure (e.g., liver and intestinal flukes, paragonimiasis, trichinosis, cysticercosis, anisakiasis, angiostrongyliasis, gnathostomiasis).

The diagnosis of a parasitic etiology for hypereosinophilia in a given patient is important for the following reasons:

• 1.

  Specific antiparasitic treatment may be indicated.

• 2.

  Prolonged hypereosinophilia can have uncomfortable and potentially life-threatening sequelae (pruritic skin rashes, painful subcutaneous swellings, endomyocardial fibrosis, and so forth).

• 3.

  The prompt search for other etiologies of hypereosinophilia may be indicated (e.g., allergy, occult tumor, leukemia, connective tissue disease, sarcoidosis, hypereosinophilic syndrome).

Laboratory Studies in Eosinophilia

It is important to consider the long prepatent period of many helminth infections before the appearance of eggs or larvae in the stool or other body fluids or tissue. For intestinal helminths and protozoa, a series of three stool examinations (one every other day) should be collected in a preservative and examined by direct, concentration, and stained slide methods. Examinations of small bowel fluid taken via nasogastric tube or endoscopy, the string test (Enterotest), or small bowel biopsy may be required to confirm infection with Strongyloides stercoralis , hookworms, liver flukes, Trichostrongylus species, or the protozoan Isospora belli . Rectal biopsy has been used to diagnose cryptic cases of schistosomiasis species, including Schistosoma haematobium .

Filariasis infections of the blood can be diagnosed by concentration or microfilter examinations of blood taken at midday for all species except Wuchereria bancrofti , whose nocturnal periodicity makes midnight blood specimens optimal. A provocative challenge with a daytime dose of 100 mg of diethylcarbamazine and drawing blood 1 hour later can increase the number of W. bancrofti microfilariae to approximate midnight blood levels. For skin filariae, skin snips or biopsy specimens often reveal microfilariae ( Chapter 47 ).

Sputum examination is useful in the detection of Paragonimus eggs and occasionally Strongyloides or Ascaris larvae. Eosinophils and Charcot-Leyden crystals in the sputum can suggest a pulmonary helminth larval migration, asthma and other nonparasitic allergic disorders, or a hypereosoniphilic syndrome. Eosinophilic pleural effusion can signify a pulmonary parasitic infection and various other causes of systemic and pulmonary eosinophilia.

The presence of eosinophils in the cerebrospinal fluid (CSF) is such an uncommon finding that it is most often the result of certain helminthic infections of the CNS. Parasitic infections to be considered in a returnee from the tropics with this finding include gnathostomiasis, cerebral cysticercosis, schistosomiasis, paragonimiasis, echinococcosis, and angiostrongyliasis. On the other hand, the absence of eosinophils in the CSF cannot rule out a CNS helminthic infection. Nonparasitic causes of CSF eosinophilia include tuberculosis, syphilis, coccidioidomycosis, viral infection, malignancy, and drug hypersensitivity, among others.

Charcot-Leyden crystals in the stool can be seen with a range of parasitic and noninfectious causes of bowel diseases. These crystals are hallmarks of eosinophil involvement in some tissue reactions. They are seen in amebic dysentery, and although not necessarily diagnostic, they may constitute a useful indicator. Charcot-Leyden crystals are also seen in the stool of patients with Trichuris trichiura and I. belli infections as well as in those with ulcerative colitis and carcinoma of the colon. They may also be seen in granulomas associated with tissue-invading helminths.

Radiologic examinations are useful diagnostic aids. Chest radiographs can give evidence for pulmonary invasive infections such as migrating Ascaris and Strongyloides larvae, paragonimiasis, acute schistosomiasis, hydatid cyst, and tropical pulmonary eosinophilia. Ultrasound studies or computed tomography scans of the liver can identify lesions that are suggestive of early prepatent liver fluke infections or hydatid cyst. Soft tissue radiographs can identify calcified cysticerci. Radiographic imaging studies (computed tomography, magnetic resonance imaging) of the brain can reveal the presence of lesions compatible with invasive cerebral parasites such as cysticercosis, hydatid cyst, paragonimiasis, and schistosomiasis.

Serologic tests, not all commercially available, can provide evidence for the presence of particular helminth infections. Serologic tests are available from the Centers for Disease Control and Prevention (CDC) for strongyloidiasis, trichinosis, cysticercosis, schistosomiasis, paragonimiasis, toxocariasis, and echinococcosis. Serum and tissue specimens are submitted to the CDC through the state public health department or through direct consultation with CDC parasitology consultants ( http://www.cdc.gov ). Filariasis serology may be obtained from the Laboratory of Parasitic Diseases of the National Institutes of Health. Fasciola hepatica serology is performed at the University of Puerto Rico. A reliable gnathostomiasis test is available at the Department of Tropical Medicine, Mahidol University, Bangkok, Thailand ( Table 49.2 ).

Specific Infections