- Parasitic Infections
II. Diagnostic Approach
- a. The immigrant/traveller with exposure to a parasite endemic region
b. The patient with no history of travel outside the US
III. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem
- IV. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem
- V. Management of parasitic infections
Medical parasitology is primarily concerned with organisms that infect the human host and may cause symptomatic or asymptomatic diseases. Three main classes of parasites cause disease in humans: protozoa - microscopic organisms that live in the blood or stool, helminths-multi-cellular organisms that can either cause systemic tissue invasive infection or establish infection in the gut, and ectoparasites that burrow in the skin causing prolonged infections (weeks to months).
Although the prevalence of parasitic infections in the US is not as widespread of a problem as the rest of the world, there are pockets of infection in the Mississippi Delta, disadvantaged urban areas, near the US-Mexico borderlands, and Appalachia where these infections cluster with poverty and presumably poor sanitation. Moreover, these infections can remain underdiagnosed if the clinician does not think of parasitic diseases in immigrants/travellers from areas of the world which are endemic for these infections.
US health professionals should be aware of the five "neglected parasitic infections" - Chagas disease, toxocariasis, cysticercosis, toxoplasmosis, and trichomoniasis that have been targeted by as public health priorities based on the large number of people affected, the severe morbidity caused and the availability of treatment and prevention.
Lastly, physicians should be cognizant of "delusional parasitosis" characterized by the fixed belief of being infested with parasites against all medical evidence to prevent unnecessary medical work-up for parasitic infection. Details of this disorder are beyond the scope of this chapter, but have been summarized in several excellent reviews.
II. Diagnostic Approach
Consideration of parasitic infection and further work-up is determined primarily by whether the patient is an immigrant from, or has recently travelled to a region endemic for parasites. The differential diagnosis in these patients vs. someone who has never travelled outside the US is broader. A good clinical history and focused physical examination can narrow the diagnosis and prevent unnecessary testing.
Common symptoms warranting consideration of specific parasitic infections in the immigrant/returning traveller are presented first. A distinction should be made between parasitic infections that can present as severe acute illness and those that cause more chronic disease. Important geographical considerations to keep in mind are:
Chloroquine resistant falciparum malaria should be assumed in a patient suspected of having malaria unless the patient is from Central America west of the Panama Canal, Haiti, the Dominican Republic, and most of the Middle East.
Chagas disease has not been reported to occur in Africa or Asia.
Of the filarial infections, onchocerciasis has been eliminated in most of Latin America except Venezuela and Brazil.
Loasis (eye worm infection) is not reported in Latin America.
Symptomatic presentations of diseases endemic to the US are presented separately.
a. The immigrant/traveller with exposure to a parasite endemic region
Fever is probably the most common nonspecific complaint and the most important infection to assess and rule out in this population is malaria. Since malaria caused by Plasmodium falciparum can be severe and cause complications, prompt workup and assessment of parasite burden in the blood is warranted. Important information is patient's country of origin/travel, duration of symptoms (Plasmodium vivax and Plasmodium ovale can relapse after months to years if not treated with radical cure).
Although classic teaching has been based on fever patterns, these may be irregular in patients with P. falciparum (especially if taking malaria prophylaxis therapy). Clinicians requiring assistance with diagnosis and management of malaria cases can call the CDC Malaria Hotline at 770-488-7788 or 855-856-4713 toll-free (M-F, 9am-5pm, eastern time). For emergency consultation after hours, call: 770-488-7100 and request to speak with a CDC Malaria Branch clinician.
In patients who presenting with persistent fever symptoms beyond a month after they left an endemic area, parasitic infections to consider are amebic liver abscess, African sleeping sickness fevers (Trypanosoma brucei subsp. - almost exclusively Africa), visceral leishmaniasis (mainly in the Indian subcontinent, Middle East, and Latin America), schistosomiasis (Africa, Middle East, Southeast Asia, and Latin America), lymphatic filariasis (sub-Saharan Africa, Southeast Asia, the western Pacific, Haiti and the Dominican Republic in the Caribbean, and coastal areas of Brazil and Guyana), and fasciolopsis (Southeast Asia).
Katayama syndrome, or "snail fever", is acute schistosomiasis with itching and diarrhea that occurs almost exclusively in travellers to endemic regions within 2 months of lake water exposure.
Nematodes such as Ascaris lumbricoides, Trichinella spiralis, and Toxocariasis (infection with flatworm) are also known to cause fevers.
Diarrhea is most commonly associated with the intestinal parasites. Details about diarrhea can help narrow the differential diagnosis of parasitic infection.
Giardia lamblia, for example, causes a chronic non-bloody, foul smelling, and greasy diarrhea with weight loss.
Entamoeba histolytica causes a bloody diarrhea even though most people infected with E. histolytica are asymptomatic.
Isospora belli and cryptosporidium are known to cause severe diarrhea in individuals who have compromised immunity, such as AIDS.
Cyclospora cayetanensis causes a watery, non-bloody diarrhea in travellers, which is often accompanied by nausea and vomiting.
Necator americanus (Hookworm) may present with diarrhea and anemia, with passage of whole or part of the worm may be noted in Ascaris and Taenia (tapeworm) infection.
Trichuris trichiura (Whipworm) infections present with rectal prolapse, and Strongyloides stercoralis,Capillaria, and Schistosoma infections can present with diarrhea, abdominal pain, and weight loss although they are often asymptomatic and may present only with eosinophilia.
Additionally, parasitic infections (E. histolytica and Angiostrongylus) can present as an abdominal mass. Hydatid cyst disease can present as asymptomatic mass lesion in the liver. Chronic Chagas disease (Trypanosoma cruzi) can present with megacolon. Mucocutaneous lesions can be caused by leishmaniasis.
Timeline of presentation after exposure is very important in assessing cutaneous syndromes. Myaisis (produced by cutaneous invasion of larvae of the bot fly in Latin America and tumbu fly in Africa) often presents with papules, nodules, and subcutaneous swellings with or without pain. This can occur within weeks to a few months after exposure. Helminth infections can persist for years to months and typically present late after exposure.
Expatriates to Loa loa endemic areas of Africa are more likely to develop cutaneous hypersensitivity reactions to the parasite compared to locals. Chronic itching and eosinophilia in subjects from endemic areas of Africa might be the only presentation of Loa or the related parasite Onchocerca volvulus. Skin nodules can help distinguish the latter. Roundworms causing lymphatic filariasis can present with skin rash and lymphadenopathy or elephantiasis. Schistosoma dermatitis is a pruritic, papular rash found on skin of travellers exposed to the parasite-containing waters.
Macular and papular eruptions that migrate might also be associated with Strongyloides, cutaneous larva migrans, and human hookworm infections as the worms penetrate the skin. Enterobius vermicularis (pinworm) causes severe perianal itching.
Symptoms of cough, dyspnea and wheezing with eosinophilia occurs due to infection with the filarial parasite Wuchereria bancrofti, but can also be seen with migration into the lung of larvae of Ascaris, hookworm, or Strongyloides. Invasion of the pulmonary parenchyma with formation of cavitary lesions can occur with parasites that can invade the lung directly like paragonomiasis and echinococcosis.
Acute ocular presentations of parasitic infections are mostly limited to visual loss caused by Toxoplasma gondii. The parasite mostly infects newborns, infants, and immunocompromised individuals and causes chorioretinitis. Toxocariasis also causes chorioretinitis and vision loss. A disconcerting presentation is migrating adult Loa loa worms noted by the patient on their conjunctiva. O. volvulus may lead to blindness due to an inflammatory response and high parasite burden; this is the condition commonly referred to as River Blindness. This is seen almost exclusively in areas endemic for this parasite.
Parasitic infections can present as meningitis. Angiostrongyliasis and gnathostomiasis cause disease by direct invasion of the meninges and cause eosinophilic meningitis. Meningitis due to Strongyloides infection occurs almost exclusively in exposed patients treated with steroids or with concurrent HTLV-1 infection.
Severe falciparum malaria can cause encephalitis. Brain mass lesions caused by neurocysticercosis should be thought of in patients from endemic areas (especially Latin America) who present with seizures or symptoms of raised intracranial pressure.
Schistosomal infections can cause a tropical spastic paraplegia. Lethal infections can be caused by Naegleria fowleri and Acanthameba can occur by exposure in the US and are discussed in section b.
Less common symptoms include heart arrhythmias (secondary to myocarditis from American Trypanosomiasis, a.k.a. Chagas disease).
b. The patient with no history of travel outside the US
The differential diagnosis of parasitic infection is limited in such a patient. It is now recognized that several neglected parasitic infections are reported in the southern US.
Of these important infections are toxocariasis. Highest age-adjusted seroprevalence is seen among non-Hispanic blacks (21.2%) and associated with low education, poverty, elevated lead concentrations, dog ownership, and living in the South or Northeast areas of the country. The parasite can cause fever, eosinophilia, and hepatomegaly in toddlers or ocular larva migrans vision loss in older children.
Neurocysticercosis can occur in US subjects with no history of exposure to pigs as evidenced by the outbreak in a Jewish community of New York. This occurs because of transmission of the embryonated eggs from a Taenia-infected person into the food.
Toxoplasmosis can cause retinochoroiditis in children and mass lesions of the brain in HIV infected US adults. Primary amebic meningoencephalitis caused by N. fowleri, Balamuthia mandrillaris, and Acanthamoeba though rare is fatal in most cases and occurs primarily in the southern United States. A history of exposure to warm water environments is almost always present.
The triatomine vectors for Chagas disease are widespread in the southern US, but few cases of chronic Chagas in non-travellers have been reported. Nevertheless, this disease should be considered in the patient from rural southern US with history of outdoor activities presenting with symptoms of cardiac disease in the southern US.
Trichomonas vaginalis symptoms include burning while urinating, painful vaginitis, and yellow frothy vaginal discharge. Cryptosporidiosis and giardiasis are also prevalent in the US (especially northern US) and show increased incidence in the summer months linked to recreational water use.
Paragonomiasis has been reported in the state of Missouri from eating of raw crayfish and these patients with cough, fever, and eosinophilia. Babesiosis is a zoonotic protozoon with transmission in the north-east United States. Clinicians should be careful not to confuse Babesia for P. falciparum in blood smears as clinical symptoms can mimic malaria.
III. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem
Physical examination is often not useful in detecting parasitic infections. However, the body site where parasites are recovered can play an important role in identifying the organism. Important examples are as follows:
Hepatosplenomegaly in malaria, visceral leishmaniasis.
Skin nodules in onchocerciasis.
Pruritic eruptions especially around the thighs and buttocks in cutaneous larva migrans and strongyloidiasis.
Diagnosis of toxoplasmosis can be made by examination of the retina of the eye.
Enterobius vermicularis (pinworm) eggs can be found in the anal area of the patients. Placing scotch tape firmly on the perianal area will pick up eggs that can be viewed in the microscope.
Neurocysticercosis can cause signs of raised intracranial pressure.
IV. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem
Laboratory testing should always be guided by the patient's history of exposure and clinical presentation.
Basic laboratory tests such as CBC and CMP should be done first to evaluate conditions such as eosinophilia (intestinal helminth infections, especially strongyloidiasis), anemia (hookworm, malaria), and leukocytosis, as all these are clues towards diagnosis.
Imaging can be particularly useful for parasites presenting with mass lesions (e.g., CT scan and MRI for cysts of Taenia in the brain, CT abdomen for hydatid cysts or amebic liver abscess, or CT chest for mass lesion in the lung from Paragonomiasis).
Scrotal ultrasound might be helpful for diagnosing lymphatic filariasis if a viable worm (filarial dance sign) is seen.
An overview of diagnostic testing from specimens obtained from different body sites is presented below.
In intestinal infections, both a simple wet mount and stained smear of the stool is often adequate. A wet mount is often helpful for examining helminth eggs, motile protozoa, trophozoites, and protozoan cysts. Some parasites, however, are passed in the feces intermittently, and therefore, multiple specimens are required for diagnosis. Thus, three stool O&P should be sent for each assessment. In addition, AIDS patients with diarrhea should be specifically tested for cryptosporidia, cyclospora, isospora, and microsporidia.
The stool specimen is the most common test. The direct wet mount is used to detect motile protozoan trophozoites. Larvae and larger helminthes eggs are examined at higher magnification. The second part of the O&P is used to recover protozoan cysts, coccidian oocytes, microsporidial spores, and helminthes eggs and larvae. The permanent stained smear is designed to help in identification of intestinal protozoa.
At times specimens other than stool must be examined. For example, small bowel infections such as giardiasis and strongyloidiasis, may require a bowel biopsy to confirm the diagnosis. The same applies for large bowel parasites such as E. histolytica and Schistosoma mansoni, which may require sigmoidoscopy with a biopsy of suspect lesions. Eggs of tapeworms (Taenia spp.) and pinworms (Enterbius) may be found on the perineal skin when they are absent from the stool.
Most recently, multiplexed stool PCR has been gaining popularity for diagnosis of intestinal helminths as well as protozoa infections and is proving to be more sensitive and specific than the traditional stool O&P. The additional advantage with PCR based tests is the increased detection rate of polyparasitism. These tests are, however, currently not widely available.
Examination of wet mount of vaginal and urethral discharges are used to identify T. vaginalis species. Examination of urinary sediment be important in identifying certain filarial infections such as microfilaria. Membrane filtration is the recommended technique for the recovery of microfilaria in urine. Centrifugation is also used for detection of Schistosoma eggs in urine samples.
Biopsy can be used for detection of parasitic infections in skin (onchocerciasis), muscle (trichinellosis), intestine (ameboma), brain (neurocysticercosis), liver (hydatid cysts) Biopsy should only be used to confirm an infection. Special precautions are needed prior to biopsy of a hydatid cyst because of the risk of anaphylactic reactions from leakage of the cyst fluid. Consultation with an expert is recommended.
Blood and tissue parasites are often more difficult to identify. Giemsa staining of blood smears is recommended for all blood parasites. Direct examination of the blood is also useful for the detection of malarial parasites even though it is usually not possible to identify malaria organisms to the species level via direct examination. Buffy coat blood films are good for detecting moving trypanosomes, microfilariae, and filarial progeny (microfilaria).
The most common stains are the Wright's stain and the Giemsa stain. The recommended stain is the Giemsa stain. In some cases, the Giemsa stain does not stain properly to allow differentiation of the microfilaria. In these cases, a Delafield stain is useful for detection of microfilaria species. Buffy coat films are used for trypanosomes which concentrate themselves within the buffy coat. Leishmania species are often found in the large mononuclear cells in the Buffy coat and are light blue cytoplasm with dark purple-red nuclear material.
Due to increased sensitivity and specificity of these tests, currently reliable serologic procedures are available for amebiasis, cysticercosis, echinococcosis, paragonomiasis, schistosomiasis, strongyloidiasis, toxocariasis, toxoplasmosis, trypanosomiasis, and trichinosis. It is recommended that these tests be performed at a testing center that has expertise in validation and use of these tests. Guidance can be obtained in this matter from the CDC.
Many laboratories do not culture specific parasites because it is often complex and not feasible for a routine diagnostic laboratory. E. histolytica,N. fowleri, Trichmonas, T. gondii, Trypanosoma, and Leishmania can be cultured if needed.
Other techniques for the detection of parasitic antigens in blood, body fluids, and tissues also have been developed. Immunfluorescent and immunosorbent kits are now commonly available for Pneumocystis jirovecii (pulmonary secretions); T. vaginalis (genitourinary fluid); and E. histolytica, Giardia, and Cryptosporidium (feces).
Polymerase chain reaction
Polymerase chain reaction (PCR) can be used for detection of many parasite stages. However, more traditional techniques such as microscopy are generally less expensive and technically demanding than PCR. PCR is useful in cases where high sensitivity is needed because of low parasite levels such as cutaneous leishmaniasis, or when species or subspecies of organisms that are morphologically indistinguishable need to be identified.
V. Management of parasitic infections
In general, malaria is one of the few parasitic infections where urgent drug therapy should be considered. Most other parasitic infections usually allow the clinician sufficient time to wait for a full confirmatory diagnostic work-up before initiating treatment.
Chloroquine and primaquine: are used in combination to treat against only chloroquine sensitive malaria (P. malariae, P. vivax, and P. ovale). Side effects include vision loss, GI disturbances, and acute hemolytic anemia in G-6-P-D deficient individuals. P. falciparum should not be treated with these drugs unless it is established that the patient is from an area with chloroquine sensitive malaria (see above). Primaquine is only used nowadays to eliminate the persistent liver phase of P. malariae and P. vivax.
Mefloquine and quinine: are used to treat chloroquine-resistant P. falciparum. Side effects include nausea, vomiting, dizziness. Hearing loss has been associated with quinine and vivid dreams with mefloquine.
Nifurtimox, melarsoprol, and suramin: are used to treat Trypanosoma species. In cases with African sleeping sickness without neurologic symptoms, suramin should be used. Melarsoprol should be used if neurologic symptoms are seen. In cases of acute American trypanosomiasis (T. cruzi) the drug of choice is nifurtimox. Nifurtimox has little effect in chronic Chagas disease. All of these drugs have toxicities associated with them and Melarsoprol especially, can cause convulsions, fever, loss of consciousness, rashes, bloody stools, nausea, and vomiting.
Metronidazole: is used to treat T. vaginalis, Giardia lamblia and E. histolytica. Patients should be cautioned against alcohol consumption using Metronidazole due to disulfram like reaction. This medication can also cause a metallic taste in mouth. Metronidazole should be followed by a luminal agent (such as paromomycin, diiodohydroxyquin, or diloxanide furoate) to eliminate intraluminal cysts in E. histoytica infections.
Nitazoxanide: is used for Cryptosporidium and Giardia lamblia. Symptoms include gastrointestinal disturbances.
Albendazole, Mebendazole, and Thiabendazole: these drugs are used for intestinal nematodes, Microsporidia, A. lumbricoides, S. stercoralis, Necator americanus (hookworm), Trichuris spiralis, T. trichiura (whipworm), and Enterbius vermicularis (pinworms). Albendazole is used to treat Taenia solium. Side effects include abdominal pain, raised liver enzymes and granulocytopenia with chronic use of albendazole. In patients presenting with subarachnoid neurocysticercosis expert consultation for concomitant steroid use should be sought before starting albendazole because severe headaches can result from cyst killing and degeneration in this form of the disease with this drug.
Ivermectin: is also used for intestinal nematodes such as A. lumbricoides, T. spiralis, T. trichiura (whipworm), S. stercoralis, and E. vermicularis (pinworms), and also is the drug of choice for O. volvulus (river blindness). Ivermectin has become the preferred agent for treatment of Strongyloides infections. In patients with suspected onchocerciasis testing for concurrent Loa loa infection should always be performed first before initiating ivermectin as inadvertent use of this drug in co-infected patients has caused severe reactions (including encephalopathy and renal failure).
Diethylcarbamazine: is used for extraintestinal nematodes such as Loa loa, O. volvulus, Brugia malayi, Wuchereria bancrofti, and toxocariasis. Side effects are caused by the death of parasites, and include muscle aches, fever, and headaches.
Praziquantel and niclosamide: are used to treat cestodes (tapeworms), trematodes (Flukes) and T. solium. Niclosamide is used as a second choice for tapeworm infections after praziquantel. Side effects include fever, diarrhea, abdominal pain, nausea, and vomiting.
Surgery should be considered in well-defined hydatid cystic disease to decrease disease burden and effect cure as treatment with anti-helminthics (albendazole) takes a long time and increases risk of side effects. PAIR (puncture, aspiration, injection, reaspiration) is a percutaneous procedure performed by experienced interventional radiologists, and is the preferred procedure in single hydatid cysts of the liver compared to surgery. Appropriate expert consultation should be sought.
Neurosurgical removal of third ventricle cysts should be considered in patients with intraventricular neurocysticercosis especially if the cyst is obstructing CSF flow and causing hydrocephalus.
IV. What's the evidence?
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Craig, MH, Bredenkamp, BL, Williams, CH, Rossouw, EJ. "Field and laboratory comparative evaluation of ten rapid malaria diagnostic tests". Trans. R. Soc. Trop. Med. Hyg.. vol. 96. 2002. pp. 258-265.
Guerrant, R. "Tropical Infectious Diseases". 2011.
Cantey, PT. "The United States Trypanosoma cruzi Infection Study: evidence for vector borne transmission of the parasite that causes Chagas disease among United States blood donors". Transfusion. vol. 52. 2012. pp. 1922-30.
Congdon, P, Lloyd, P. "Toxocara infection in the United States: the relevance of poverty, geography and demography as risk factors, and implications for estimating county prevalence". Int J Public Health. vol. 56. 2011. pp. 15-24.
Hotez, PJ. "Neglected infections of poverty in the United States of America". PLoS Negl Trop Dis. vol. 2. 2008. pp. e256.
Schantz, PM. "Neurocysticercosis in an Orthodox Jewish community in New York City". N Engl J Med. vol. 327. 1992. pp. 692-5.
Foth, BJ, McFadden, GI. "The apicoplast: a plastid in Plasmodium falciparum and other Apicomplexan parasites". Int. Rev. Cytol.. vol. 224. 2003. pp. 57-110.
Garcia, LS. "Diagnostic Medical Parasitology". ASM Press. 2001.
Garcia, LS, Shimizu, RY, Brewer, TC, Bruckner, DA. "Evaluation of intestinal parasite morphology in polyvinyl alcohol preservative: comparison of copper sulfate and mercuric chloride base for use in Schaudinn's fixative". J. Clin. Microbiol. vol. 17. 1983. pp. 1092-1095.
Isenberg, HD. "Clinical Microbiology Procedures Handbook". vol. 1, 2, and 3. ASM Press. 2004.
Krishna, S, White, NJ. "Pharmacokinetics of quinine, chloroquine and amodiaquine". Clinical implications. Clin. Pharmacokinet. vol. 30. 1996. pp. 263-299.
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Smith, JW, Gutierrez, Y, Henry, JB. "Clinical Diagnosis and Management by Laboratory Methods". The W. B. Saunders Company. 1991.
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