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Approach to Parasitic Infections

By Richard D. Pearson, MD, Professor of Medicine and Pathology, Associate Dean for Student Affairs, University of Virginia School of Medicine

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Human parasites are organisms that live on or in a person and derive nutrients from that person (its host). There are 3 types of parasites:

  • Single-cell protozoa

  • Multicellular helminths (worms)

  • Ectoparasites such as scabies and lice

Parasitic infections due to protozoa and helminths are responsible for substantial morbidity and mortality worldwide. They are prevalent in Central and South America, Africa, and Asia. They are much less common in Australia, Canada, Europe, Japan, New Zealand, and the US. By far, the greatest impact is on residents of impoverished tropical areas with poor sanitation, but parasitic infections are encountered in developed countries among immigrants and travelers returning from endemic regions and, on occasion, even among residents who have not traveled, particularly those with AIDS or other conditions that cause immunodeficiency.

Many parasitic infections are spread through fecal contamination of food or water. They are most frequent in areas where sanitation and hygiene are poor. Some parasites, such as the hookworm, can enter the skin during contact with contaminated dirt or, in the case of schistosomes, with freshwater. Others, such as malaria, are transmitted by arthropod vectors. Rarely, parasites are transmitted via blood transfusions or shared needles or congenitally from mother to fetus.

Some parasites are endemic in the US and other developed countries. Examples are the pinworm Enterobius vermicularis, Trichomonas vaginalis, Toxoplasma gondii, and enteric parasites such as Giardia intestinalis (also known as G. duodenalis or G. lamblia) and Cryptosporidium spp.

The characteristics of protozoan and helminthic infections vary in important ways.

Protozoa

Protozoa are single-celled organisms that multiply by simple binary division (see Intestinal Protozoa and Microsporidia and Extraintestinal Protozoa). Protozoa can multiply in their human hosts, increasing in number to cause overwhelming infection. With rare exceptions, protozoan infections do not cause eosinophilia.

Helminths

Helminths are multicellular and have complex organ systems. Helminths can be further divided into

Some parasites have adapted to living in the lumen of the intestine where conditions are anaerobic; others reside in blood or tissues in aerobic conditions.

In contrast to protozoa, helminths do not multiply in humans but can elicit eosinophilic responses when they migrate through tissue. Most helminths have complex life cycles that involve substantial time outside their human hosts. A few, including Strongyloides stercoralis, Capillaria philippinensis, and Hymenolepis nana, can increase in number because of autoinfection (offspring reinfect the same host rather than being shed to infect another host). In strongyloidiasis, autoinfection can result in life-threatening, disseminated hyperinfections in immunosuppressed people, particularly those taking corticosteroids.

The severity of helminthic infections usually correlates with the worm burden, but there are exceptions as when a single ascaris causes life-threatening pancreatitis by migrating into and obstructing the pancreatic duct. The worm burden depends on the degree of environmental exposure, parasite factors, and the host’s genetically determined immune responses. If a person moves from an endemic area, the number of adult worms diminishes over time. Although a few parasites (eg, Clonorchis sinensis) can survive for decades, many species have life spans of only a few years or less.

Nematodes are nonsegmented cylindric worms ranging from 1 mm to 1 m in length. Nematodes have a body cavity, distinguishing them from tapeworms and flukes. Depending on the species, different stages in the life cycle are infectious to humans. Hundreds of millions of humans are infected with nematodes; the most common are Ascaris (ascariasis), hookworms, and Trichuris (trichuriasis).

Cestodes (tapeworms) as adults are multisegmented flatworms that lack a digestive tract and absorb nutrients directly from the host’s small bowel. In the host’s digestive tract, adult tapeworms can become large, up to 40 m for one species. Tapeworms that infect humans include the fish tapeworm (Diphyllobothrium latum), beef tapeworm (Taenia saginata), and pork tapeworm (Taenia solium).

Trematodes (flukes) are nonsegmented flatworms that infect the blood vessels, GI tract, lungs, or liver. They are usually no more than a few centimeters in length; however, some are only 1 mm, and some are as large as 7 cm. In humans, most fluke infections are caused by Schistosoma sp (schistosomiasis), Paragonimus westermani (paragonimiasis), and Clonorchis sinensis (clonorchiasis).

Microsporidia

Microsporidia are intracellular spore-forming organisms that used to be classified as protozoa, but genetic analysis indicates that they are fungi or closely related to them. Human disease is mainly limited to people who have AIDS or another severe immunocompromising conditions. The clinical manifestations include gastroenteritis, focal involvement of the eyes, and disseminated infection.

Diagnosis

  • Microscopic examination

  • Antigen and DNA tests

Methods used to diagnose specific parasitic diseases are summarized in Collecting and Handling Specimens for Microscopic Diagnosis of Parasitic Infections*. (see also specific infections elsewhere in The Manual).

Parasitic infections should be considered in the differential diagnosis of clinical syndromes in residents of or travelers to areas where sanitation and hygiene are poor or where vector-borne diseases are endemic. For example, fever in the returning traveler suggests the possibility of malaria. Experience indicates that people who have immigrated from endemic areas to developed countries and who return home to visit friends and relatives are at particular risk. They frequently do not seek or cannot afford pretravel advice on disease prevention and are more likely to enter high-risk settings than tourists who stay at resort facilities.

Although less frequent, the possibility of an endemic or imported parasitic infection must also be considered in residents of developed countries who present with suggestive clinical syndromes, even if they have not traveled.

Historical information, physical findings, and laboratory data may also suggest specific parasitic infections. For example, eosinophilia is common when helminths migrate through tissue and suggests a parasitic infection in an immigrant or returning traveler.

The diagnosis of parasitic infections was once based on the identification of ova, larvae, or adult parasites in stool, blood, tissue or other samples or the presence of antibodies in serum, but diagnosis is being increasingly based on identification of parasite antigens or molecular tests for parasite DNA.

Physicians with expertise in parasitic infections and tropical medicine are available for consultation at many major medical centers, travel clinics, and public health facilities.

For detailed descriptions of diagnostic methods, see the CDC's Laboratory Identification of Parasites of Public Health Concern.

Collecting and Handling Specimens for Microscopic Diagnosis of Parasitic Infections*

Parasite

Optimal Specimen

Collection Details

Comments

Blood

Plasmodium sp

Thick and thin smears of capillary blood (ie, finger or earlobe, using a disposable lancet) or 5–10 mL of fresh anticoagulated blood (preferably in collection tubes that contain EDTA)

Collect multiple samples during acute illness.

Prepare smears from capillary or anticoagulated blood within 3 h after collection.

.

Use Wright or Giemsa stain.

Ensure that glass slides are clean.

Babesia sp

Thick and thin smears as for Plasmodium sp

Collect as for Plasmodium sp.

Use Wright or Giemsa stain.

Morphology is similar to Plasmodium sp ring forms but without pigment and gametocytes. Tetrads are diagnostic of Babesia sp but are infrequent.

Trypanosoma sp

Thin smears of capillary blood or 5–6 mL of anticoagulated blood

Collect capillary or anticoagulated blood. Smear on glass slides.

Various concentration techniques are used to enhance sensitivity.

Motile trypanosomes are seen in wet preparations; Giemsa (or Field) stain is used to identify them in fixed preparations.

Filarial worms

Thick and thin smears from 1 mL of anticoagulated blood; if first specimen is negative, 5–10 mL, concentrated by centrifugation or filtration

Microfilariae of Wuchereria bancrofti and Brugia malayi: Draw blood between 10 pm and 2 am.

Loa loa, Dipetalonema perstans, and Mansonella ozzardi: Draw blood between 10 am and 6 pm.

Use Giemsa or hematoxylin-eosin stain directly or, for greater sensitivity, after concentration in 2% formalin (Knott technique) or after filtration through a Nucleopore® membrane.

Bone marrow, other reticuloendothelial tissue, or CSF

Leishmania sp

Aspirates of bone marrow, spleen, liver, or lymph nodes or smears from the buffy coat

Smear on glass slides.

Use Giemsa, Wright-Giemsa, or hematoxylin-eosin stain.

Naegleria

Acanthamoeba

Balamuthia

Fresh spinal fluid

Use aseptic collection technique.

Examine specimen as soon as possible.

Examine using light or phase-contrast microscopy.

Parasites may be detected by their movements; they can be fixed and stained with Giemsa or cultured.

Trypanosoma brucei gambiense and rhodesiense

Aspirates of lymph nodes or chancre

Fresh spinal fluid

Use aseptic collection technique.

Use wet mount to identify motile parasites, or fix and stain with Giemsa or Field stain before or after concentration by centrifugation.

Duodenal aspirate or jejunal biopsy

Giardia sp

Cryptosporidium sp

Cystoisospora sp

Cyclospora sp

Microsporidia

Strongyloides sp

Duodenal aspirate or jejunal biopsy specimen

Examine aspirates immediately, or fix and stain them. Do histopathologic examination of biopsy specimens.

Use a wet mount of aspirate to identify ova or Strongyloides larvae. Multiple stains may be used for diagnosis (see Feces below for details).

Transmission electron microscopy is the gold standard for detection of microsporidia.

Rectal biopsy

Schistosoma mansoni

Schistosoma japonicum

Rectal biopsy specimen from level of dorsal fold (Houston valve), about 9 cm from anus

Fix for histopathologic examination, and crush a segment between slides for increased sensitivity.

Speciation is based on the morphology of ova.

Sigmoidoscopy (proctoscopy)

Entamoeba histolytica

Fresh scrapings with a curet or Volkmann spoon, a piece of mucosa snipped off with a surgical instrument, or aspirate from a lesion via a 1-mL serologic pipette with a rubber bulb (cotton-tipped swabs are not satisfactory)

Examine specimen immediately or after fixation and staining.

Use wet mounts or fixed stained slides (eg, with Trichrome stain) to detect trophozoites and cysts. Stool should be assayed for E. histolytica antigen; this test is more sensitive and can differentiate E. histolytica from nonpathogenic ameba.

Feces

Entamoeba histolytica

Entamoeba dispar

Entamoeba moshkovski

Other amebas

Multiple freshly passed stools (≥ 3) collected in am

Examine unformed or diarrheal specimens within 15 min.

Keep formed stools refrigerated until examination. Preserve in formalin or another fixative.

Use wet mounts and permanent stained slides (eg, Trichrome stain) and concentration techniques for cysts.

Stool should be assayed for specific E. histolytica antigen, which is more sensitive and can differentiate E. histolytica from the nonpathologic E. dispar, E. moshkovski, and other nonpathogenic organisms.

Giardia sp

Multiple freshly passed stools (≥ 3) collected in am every other day

Examine fresh, or preserve in formalin or another fixative. Trophozoites can also be detected in duodenal aspirates.

Examine direct and concentrated specimens. Cysts are usually seen in wet mounts and trophozoites are seen in fixed, Trichrome-stained slides. Assays for fecal antigens are more sensitive.

Cryptosporidium sp

Multiple freshly passed stools (≥ 3) collected daily or every other day

Refrigerate and examine fresh samples, or preserve in formalin or another fixative.

Handle with care; fresh and dichromate-preserved stools are infectious.

Duodenal aspirate or biopsy can be diagnostic.

Examine wet mounts by conventional light, differential interference contrast, and immunofluorescence microscopy.

Stain specimens with modified acid-fast or modified safranin. Assays for fecal antigens are more sensitive.

Cystoisospora sp

Multiple freshly passed stools collected daily or every other day

Examine fresh, or preserve in formalin or other fixative. Concentration techniques enhance sensitivity.

Oocysts can be visualized in wet mounts by bright-field differential interference contrast or epifluorescence microscopy. Stain fixed specimens with modified acid-fast stain. When stools are negative, examination of duodenal aspirate or a biopsy specimen can be diagnostic.

Cyclospora spp

Multiple freshly passed stools collected daily or every other day

Specimens should be refrigerated and examined fresh or frozen, or preserved in 10% formalin and 2.5% potassium dichromate. Different laboratory tests require different preservation techniques. Concentration techniques increase sensitivity.

Examine wet mounts by conventional light, bright-field differential interference contrast, and UV fluorescence microscopy. Oocysts are autofluorescent under UV light. Fixed specimens can be stained with modified acid-fast stain or modified safranin. A sporulation assay can differentiate Cyclospora from blue-green algae.

Microsporidia

Multiple stools collected daily or every other day

Small-bowel biopsies may be necessary if stools are negative.

Specimens stained by chromotropic methods are most widely used. Chemofluorescent agents such as calcofluor white can also be used for quick identification.

Electron microscopy is the most sensitive method and used for speciation.

Trichuris sp

Ascaris sp

Hookworms

Strongyloides sp

Tapeworms

Flukes

Multiple stools collected daily (up to 7 needed for Strongyloides)

Refrigerate specimen, and examine fresh, or fix in 10% formalin and concentrate using formalin–ethyl acetate sedimentation.

Active larvae are seen with Strongyloides; ova are seen with other intestinal helminths.

For Strongyloides, the agar plate assay is more sensitive than ova and parasite examination. If stool is held at ambient temperature, Strongyloides larvae may appear similar to hatched hookworm larvae.

Enterobius sp

Ova collected from area around the anus on cellophane tape and placed on glass slide

Collect from area around the anus in the am before a bowel movement or bath.

Enterobius ova are occasionally seen in a stool specimen or in vaginal contents obtained during a Papanicolaou test. Adult worms may be observed on the perianal region or in the vagina.

Sputum or aspirate from respiratory tract

Paragonimus sp

Fresh sputum

Examine specimen as soon as possible, or preserve for later examination.

Concentration techniques may be necessary. Occasionally, ova are present in pleural fluid.

Strongyloides sp (hyperinfection)

Sputum, any aspirated material, fluid obtained by BAL or drainage material

Examine specimen as soon as possible, or preserve it for later examination.

Active larvae may be seen in wet mounts or can be fixed and stained with Giemsa.

Lung biopsy

Paragonimus sp

Open lung biopsy or

percutaneous biopsy guided by fluoroscopy or CT

Collect and place in sterile container with sterile saline. Fix and stain with Giemsa or hematoxylin-eosin.

Ova and adult flukes can be identified.

Skin

Onchocerca volvulus

For patients infected in Africa, skin snips from the thigh, buttocks, or iliac crest

For patients infected in Latin America, skin snips from the head, scapula, or buttocks

For skin snips, disinfect the skin with alcohol, insert a 25-gauge needle just under the epidermis, raise it, and slice off small piece of tissue with a scalpel or razor blade, or use a sclerocorneal punch biopsy tool. Bleeding should not occur. Examine fresh, or fix in methanol and stain with Giemsa or hematoxylin-eosin.

Examine the specimen suspended in saline for motile microfilaria migrating from the skin snip. Microfilariae may be seen in tissue sections.

Leishmania sp

Biopsy of a nonulcerated area of the lesion and touch preparations or slip smear scrapings

Look for amastigotes in Giemsa-stained touch preparations or smears and in hematoxylin-eosin–stained biopsy specimens.

Leishmania amastigotes are morphologically indistinguishable from those of Trypanosoma cruzi. Leishmania can be cultured from skin biopsies, but growth in vitro may take weeks. Molecular assays for leishmania DNA are available.

Urogenital secretions or biopsy

Trichomonas sp

Sterile swabs of vaginal, urethral, or prostatic secretions placed in a tube with a small amount of sterile saline

Tell female patients not to douche for 3–4 days before collecting the specimen.

Send specimen to the laboratory as soon as possible.

Identification of motile organisms by wet mount is the most rapid. Direct fluorescent antibody for parasites is more sensitive; culture is most sensitive but takes 3–7 days.

Schistosoma haematobium, occasionally S. japonicum

Fresh urine or biopsy from the area around the trigone

Recommended time for urine collection is between noon and 3 pm. Centrifugation increases detection.

Ova can be seen in wet mounts of urine or in biopsy specimens from the bladder.

BAL = bronchoalveolar lavage; EDTA = ethylene diamine tetraacetic acid; UV = ultraviolet.

Based on the CDC: Laboratory Identification of Parasitic Diseases of Public Health Concern, which provides detailed instructions.

GI tract parasites

Various stages of protozoa and helminths that infect the GI tract are typically shed in the stool. Routine detection requires examination of stool specimens, preferably 3 collected on different days, because shedding can vary. Sensitivity of stool examination for ova and parasites is low enough that when clinical suspicion is strong, empirical treatment should be considered. Sensitive and specific assays are now available to detect antigens of G. intestinalis, Cryptosporidium spp, and Entamoeba histolytica in stool. Although expensive, molecular tests for G. intestinalis, Cryptosporidium spp, E. histolytica, and Cyclospora are included in PCR-based screens for enteric bacterial, viral, and parasitic pathogens in stool samples (see Table: Serologic and Molecular Tests for Parasitic Infections).

Freshly passed stools uncontaminated with urine, water, dirt, or disinfectants should be sent to the laboratory within 1 h; unformed or watery stools are most likely to contain motile trophozoites. If not examined immediately, stools should be refrigerated, but not frozen. Portions of fresh stools should also be emulsified in fixative to preserve GI protozoa. Concentration techniques can be used to improve sensitivity. Anal cellophane tape or swabs may collect pinworm or tapeworm eggs. If strongyloidiasis is suspected, fresh stool should be smeared on an agar plate and incubated to identify the tracks of migrating larvae. Antibiotics, x-ray contrast material, purgatives, and antacids can hinder detection of ova and parasites for several weeks.

Sigmoidoscopy or colonoscopy should be considered when routine stool examinations are negative and amebiasis is suspected in patients with persistent GI symptoms. Sigmoidoscopic specimens should be collected with a curet or spoon (cotton swabs are not suitable) and processed immediately for microscopy. Duodenal aspirates or small-bowel biopsy specimens may be necessary for diagnosis of such infections as cryptosporidiosis and microsporidiosis.

Serologic testing for parasitic infections

Some parasites can be detected by serologic tests (see Table: Serologic and Molecular Tests for Parasitic Infections).

Serologic and Molecular Tests for Parasitic Infections

Infection

Antibody

Antigen or DNA/RNA

Protozoans

African trypanosomiasis (West)

CATT

Amebiasis

EIA, IHA

Stool: Antigen (EIA), PCR

Babesiosis

IFA

Blood: PCR

Chagas disease

IFA, EIA, RIPA

Blood, tissue, or CSF: PCR

Cryptosporidiosis

Stool: Antigen (EIA), PCR

Cyclosporiasis

PCR

Giardiasis

Stool: Antigen (EIA), DFA, PCR

Leishmaniasis

IFA or EIA (for visceral but not cutaneous leishmaniasis)

Blood or tissue: PCR

Malaria

IFA

Blood: ICG for antigen (rapid diagnostic test), PCR

Microsporidiosis

Stool or intestinal tissue: IFA, IIF, TEM, PCR

Toxoplasmosis

IFA, EIA (IgG and IgM)

Tissue or blood: PCR

Roundworms

Filariasis

Blood: Antigen (ICG; not available in the US)

Strongyloidiasis

EIA, IFA, IHA

Trichinellosis

EIA

Toxocariasis

EIA

Flukes

Paragonimiasis

CF, IB, EIA

Schistosomiasis

FAST-ELISA, IB

Tapeworms

Cysticercosis

IB (serum or CSF), EIA

Serum or CSF: Antigen (used to assess responses to therapy; not sensitive enough for diagnosis)

CSF: PCR

Echinococcosis

EIA, IHA, IFA, IB

CATT = card agglutination trypanosomiasis test for Trypanosoma brucei gambiense; CDC = Centers for Disease Control and Prevention; CF = complement fixation; DFA = direct fluorescent antibody; EIA = enzyme immunoassay; FAST-ELISA = Falcon assay screening test–enzyme-linked immunosorbent assay; IB = immunoblot; ICG = immunochromatographic assay; IFA = indirect fluorescent antibody test; IHA = indirect hemagglutination assay; IIF = immunofluorescence assay; PCR = polymerase chain reaction; RIPA = radioimmunoprecipitation assay; TEM = transmission electronic microscopy.

Note: Some antigen and parasite detection kits are available commercially. Others are available at the CDC or other reference laboratories. Molecular tests (eg, PCR) for DNA are available to detect enteric protozoa in stool samples, but they are expensive. Molecular tests for a number of other parasites are available in reference or research laboratories.

Treatment

  • Various treatments, depending on the specific infection

Advice for treating parasitic infections is available from experts at major medical and public health centers and travel clinics, at the CDC web site, in textbooks of infectious diseases and tropical medicine, and in summary form from The Medical Letter on Drugs and Therapeutics.

Drugs for unusual parasitic infections can often be obtained from the CDC Drug Service or the manufacturer.

Prevention

Despite substantial investment and research, no vaccines are yet available for prevention of human parasitic infections. Prevention is based on avoidance strategies.

Transmission of most intestinal parasites can be prevented by

  • Sanitary disposal of feces

  • Adequate cooking of food

  • Provision of purified water

For the international traveler, the best advice is “cook it, boil it, peel it, or forget it.” When followed, these measures reduce but do not eliminate the risk of intestinal parasitic infections as well as the risk of bacterial and viral gastroenteritis. Meat, particularly pork, and fish, particularly freshwater varieties, should be thoroughly cooked before ingestion. Other safety measures include removing cat litter boxes from areas where food is prepared to prevent toxoplasmosis. People should not swim in freshwater lakes, streams, or rivers in areas where schistosomiasis is endemic or walk barefoot or sit bare-bottom in areas where hookworms are found.

Prevention of malaria and many other vector-borne diseases involves

  • Wearing long-sleeved shirts and pants

  • Applying diethyltoluamide (DEET)-containing insect repellants to exposed skin and permethrin to clothing

  • Using window screens, air-conditioning, and mosquito nets impregnated with permethrin or other insecticides

  • For residents of nonendemic areas who travel in regions where malaria is transmitted, taking prophylactic antimalarial drugs

Travelers to rural Latin America should not sleep in adobe dwellings where reduviid bugs can transmit Chagas disease (see Chagas Disease : Prevention). In Africa, travelers should avoid bright-colored clothing and wear long-sleeved shirts and pants to avoid tsetse flies in regions where African sleeping sickness occurs (see African Trypanosomiasis : Prevention).

Country-specific recommendations for travel are available from the CDC: Travelers' Health, from the CDC: Travel Health and the Yellow Book, and in CDC Health Information for International Travel 2016.

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* This is the Professional Version. *