Keywords

Intestinal Parasitic Infections in Refugees

On October 31, 2011, this planet welcomed its seven billionth inhabitant. Of that difficult to encompass number, roughly one-third harbor a parasitic infection, more than half of which are intestinal [1]. Although many of these intestinal parasitic infections are subclinical and patients who have them are asymptomatic, they can cause significant morbidity and may result in mortality. The United States welcomes immigrants from parts of the world where people are constantly and continuously exposed to intestinal parasites, many of which are diagnosed and treated upon arrival in the US. Methodological differences in studying the prevalence of a given parasite (e.g., stool ova and parasites versus serology) as well as differing characteristics of refugees such as country of origin, age, and education level render the task of determining exact numbers of immigrants affected by intestinal parasites difficult. What we do know is that they are among the most commonly seen infections in refugees, with estimates ranging from 8.4 to 84 % of refugees in North America being affected [1, 2]. See Fig. 6.1 for prevalence of intestinal parasites in a large sample of refugees in Minnesota. Starting in 1999, the CDC began implementing recommendations for empiric antiparasitic treatment for refugees coming to the United States, both before departure and upon their arrival [3].

Fig. 6.1
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Prevalence of intestinal parasites in a large refugee sample in Minnesota (Swanson SJ et al. N Engl J Med 2012;366:1498–1507)

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As one would expect, the prevalence of intestinal parasites in newly arriving refugees, especially the nematodes causing trichuriasis, ascariasis, and hookworm infection, has been significantly impacted by the implementation of pre-departure presumptive treatment in US-bound refugees [4]. Overall, there has been a decrease in intestinal parasitosis since starting empiric pre-departure therapy, as well as a shift in the most commonly found parasites when screened upon arrival to the United States [4] (see Fig. 6.2). Prior to implementation of pre-departure empiric therapy, the most commonly encountered organisms found during screening included hookworm infection and Giardia (a protozoan), whereas since 1999 the most commonly encountered helminth has become Trichuris [4]. Subsequent data has indicated that Strongyloides, which is not adequately treated with a single dose of albendazole, and schistosomiasis, which is not treated with albendazole, were highly prevalent infections in refugees [4]. These two parasites were of particular concern since not only are they common, they also cause chronic infection and can result in serious morbidity and even mortality. In 2007 ivermectin and praziquantel (for sub-Saharan African refugees) were recommended. Praziquantel was instituted in sub-Saharan Africans in 2010 but ivermectin has not been implemented to date [3].

Fig. 6.2
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Change in intestinal parasitosis with empiric pre-departure therapy (Swanson SJ et al. N Engl J Med 2012;366:1498–1507)

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Screening Recommendations

Optimally, refugees arriving to the United States from Africa, Asia, and Southeast Asia should receive some form of presumptive therapy for intestinal parasites. This is typically performed by the International Organization for Migration (IOM) in their home countries or in refugee camps. If they have undergone presumptive therapy, new arrivals may have documentation of their treatment course.

The term “presumptive therapy” encompasses treatment for intestinal parasites which refugees coming from certain parts of the world can be “presumed” to have based on prevalence data from a given area. The principal intestinal parasites that are targeted, as well as the medications used with presumptive therapy are:

  1. 1.

    Soil-transmitted helminths (STH) including the roundworms, hookworm, Ascaris, and Trichuris (albendazole)

  2. 2.

    Strongyloides (ivermectin)

  3. 3.

    Schistosomes (praziquantel)

It is recommended that all refugees from South and Southeast Asia, except those with contraindications, be treated with albendazole and ivermectin. It is also recommended that all refugees from Africa should be treated with albendazole and praziquantel and those from non-Loa loa endemic areas with ivermectin for Strongyloides [3]. Please see Table 6.1 for a summary of these recommendations. Of particular note when considering presumptive therapy for Africans is the importance of the parasite Loa loa. In areas of Loa loa endemicity (see Table 6.2), there have been reports of encephalitis resulting from ivermectin therapy (which targets Strongyloides) in patients who have a concomitant Loa loa infection and a high microfilarial parasite load. Because of this, any patient who comes from a Loa loa endemic country should not be treated presumptively with ivermectin before coming to the United States. Rather, they should be tested for Strongyloides in the United States and if positive, treated with high-dose albendazole or screened for Loa loa with a daytime blood smear, and if negative, treated with ivermectin [3]. These recommendations are not uniformly implemented due to logistics and funding issues. An updated list of pre-departure therapy received by each major resettlement group may be found at http://www.cdc.gov/immigrantrefugeehealth/guidelines/overseas/interventions.html.

Table 6.1 Recommended medication regimen for presumptive treatment of parasitic infections [3]
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Table 6.2 Loa loa endemic countries in Africa [3]
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There are a number of important exceptions which limit receipt of presumptive therapy including pregnancy, breastfeeding, and restrictions on use of medications at young ages. Please see Table 6.3.

Table 6.3 Contraindications to presumptive therapy
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Once in the destination country, post-arrival screening recommendations are tailored to whether or not the refugee received pre-departure treatment [5]. Please see Table 6.4.

Table 6.4 Overview of post-arrival screening recommendations
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Parasites Commonly Encountered in Refugees

The most commonly found intestinal parasites seen in newly arrived refugees to the United States have changed somewhat since the introduction of albendazole pre-departure treatment in 1999. Based on data collected from Minnesota between 1993 and 2007, infection with Giardia lamblia and Trichuris are now the most prevalent intestinal parasites seen. Among the nematodes, Strongyloides, Ascaris, and hookworm are the most common behind Trichuris [4]. Of course, geographic origin will play a very important role in modifying the initial differential formed when seeing a refugee patient (see Table 6.5), especially with less common organisms such as the non-schistosome flukes (e.g., paragonimiasis) and the cestodes (e.g., Taenia spp. and Hymenolepis). A summary of common parasites encountered in refugees follows.

Table 6.5 Predominant geographic distribution of intestinal parasites found in refugee populations [5]
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Protozoa

The protozoa are single-celled organisms which cause quite similar symptoms as a group, those being abdominal discomfort and diarrhea. They are also overall more likely not to cause disease than to cause disease in those who are affected.

Entamoeba histolytica. Although a causative agent of dysentery, E. histolytica more commonly causes mild gastrointestinal disease such as abdominal discomfort and loose stools. It can cause a more severe disease which involves bloody diarrhea (dysentery) and may become tissue invasive [6]. In this latter case, the most common site is the liver, where an abscess may form. It may also affect the lungs and brain, although these presentations are rare. In refugees E. histolytica causing clinical disease after arrival to the United States is rare. Although cysts are commonly reported in stool ova and parasite examination, these cysts are much more likely to be the indistinguishable, non-pathogenic, E. dispar. When reported in an asymptomatic person the diagnosis of E. histolytica should be confirmed with a stool antigen test prior to treating.

Giardia spp. This is the most commonly encountered parasite in refugee populations who receive ova and parasite stool screening. Giardia is the most common parasitic cause of diarrhea affecting people in both developed and developing countries, the latter far more than the former. Transmitted by fecal-oral contamination, it, like many others, preferentially affects those in poorer socioeconomic areas. Most infections are asymptomatic. There is lack of data regarding benefit versus cost and risk of adverse events in treating asymptomatic persons. Those with symptoms (e.g., bloating, burping, abdominal discomfort, diarrhea, or failure to thrive in small children) should be tested for this infection and treated accordingly. Routine screening in asymptomatic persons is not recommended; however, when encountered, most clinicians choose to treat. There is no consensus on this latter point.

Blastocystis hominis. Ubiquitous throughout the world, Blastocystis is the most commonly encountered organism in screening fecal cultures in new arrivals. In most individuals, this infection does not cause signs or symptoms and is not considered a pathogen. However, it has been associated with disease in certain individuals, particularly those with underlying immunodeficiency (e.g., HIV), and in travelers. If a person has gastrointestinal symptoms and no other etiology is found, it is reasonable to consider treatment.

Dientamoeba fragilis. A common parasite, D. fragilis, can cause abdominal pain, persistent diarrhea, and flatulence which may be chronic or acute, although many who are infected have no symptoms. It is transmitted via the fecal-oral route and when symptomatic should be treated.

Nematodes

Roundworms belong to the phylum Nematoda and are therefore commonly referred to as nematodes. Among the most abundant animals on earth, they are a common cause of infection and disease in the developing world, both acute and chronic, the latter having powerful effects on development.

Soil-transmitted helminths (STH) are a group which includes Ascaris lumbricoides, Trichuris trichiura, and the hookworms. They are commonly referred to together because of their very high prevalence, similarity in life cycle, and worldwide distribution. They also belong to the group of “neglected tropical diseases,” along with several other infectious agents labeled so by the WHO because they affect a broad swath of humanity, often in developing countries, but do not garner the research and interest that other diseases often do [7, 8]. All soil-transmitted helminths need a soil cycle, and transmission in the United States is rare. They all have a limited life span, and within 5 years of leaving an endemic area, a refugee will be free of infection.

Ascaris lumbricoides (STH). The most common of the soil-transmitted helminths, nearly one in six people (roughly 1.2 billion humans) are infected [9]. The vast majority of infected individuals have no symptoms. However, with high numbers of worms, commonly referred to as a large worm burden, patients can suffer intestinal blockage. This is most common in children. In addition, the parasite may “wander” into areas where its presence may cause disease, such as blocking the gallbladder outlet (causing cholecystitis) or the appendix (causing appendicitis). Because of its life cycle, which involves passing through the lungs, patient may also present with respiratory symptoms such as cough, dyspnea, and wheezing.

Trichuris trichiura (STH). Trichuris is a parasite which inhabits the large intestine (most nematodes infect the small bowel) and is found in many areas where human feces are used as fertilizer (often referred to as “night soil”). One becomes infected by ingesting Trichuris eggs, and it can, like many other parasites, be asymptomatic or cause disease. More than 90 % of people infected are asymptomatic. Those who are symptomatic may experience watery, bloody, and painful bowel movements. In addition, it is associated with anemia. In children with heavy infections, growth retardation can occur. It has been associated with rectal prolapse.

Hookworm: Ancylostoma duodenale, Necator americanus (STH). Hookworm is found in areas where human feces are used as fertilizer or in areas where human wastes are deposited on the soil. Infection occurs via direct penetration of the skin, often of the lower extremities, and the first symptom is often an itchy rash at the site of infection. Once established in the small intestine, they can cause abdominal pain, as well as weakness and fatigue. They are most notable for the chronic anemia which may result from chronic infection, resulting in growth retardation in children. This is the most pathogenic of the soil-transmitted helminths.

Strongyloides stercoralis. Although a nematode that is very similar to hookworm, Strongyloides is generally not grouped with the other STHs. A roundworm roughly the size of a mustard seed, Strongyloides is a soil-transmitted helminth which, like Trichuris and hookworms, infects humans via skin penetration, often of the feet and legs. Found throughout the world, but predominantly in tropical areas, Strongyloides often manifests itself with dermatologic, pulmonary, and intestinal symptoms such as rash, dry cough, and abdominal discomfort.

NOTE: Unlike most other helminths, Strongyloides is capable of autoinfection, i.e., the host can continually reinfect himself/herself and thus have a persistent, even lifelong infection. Also, Strongyloides can become disseminated and result in “hyperinfection” which has a high mortality rate and is often misdiagnosed as Gram-negative sepsis; this is most often due to immunosuppression particularly following the administration of corticosteroids. Special attention must also be given when considering treatment of patients with Strongyloides who are from Loa loa endemic areas (please see Section “Screening Recommendations” above).

Loa loa. A nematode transmitted by the bite of deerflies of the genus Chrysops, loaiasis most often results in eye worm and red, itchy swellings of the skin referred to as Calabar swellings. It is found throughout west-central sub-Saharan Africa, in areas of high-canopied rain forest. One key factor making Loa loa infection of prime importance is that in patients treated with ivermectin for Strongyloides who were coinfected with Loa loa, there have been reports of encephalitis precipitated by the treatment; please see recommendations above.

Trematodes

Trematodes, also known as “flukes,” are parasites which infect many different types of vertebrate hosts, including man. Their life cycle typically involves a freshwater snail as an intermediate before infection of the definitive vertebrate host.

Schistosoma spp. Widespread throughout the tropical world, Schistosome species are very important and at times overlooked parasites which can cause significant morbidity when chronic. Schistosomes have a complex life cycle which must involve certain freshwater snails, and humans are infected via the skin, usually by wading in areas populated by said snails. Initially, patients may have a dermatologic reaction at the site of skin penetration, including rash with vesicles and pruritus. Roughly 5–7 weeks after infection, patients may develop “Katayama fever,” the syndrome of fever, headache, myalgias, abdominal pain (right upper quadrant often), and bloody diarrhea [10]. Serious neurologic complications can also occur at this time, including seizures and transverse myelitis. Untreated infections, which may last many years, lead to a chronic granulomatous disease which can cause liver disease and large intestinal symptoms with S. mansoni, S. japonicum, and S. mekongi, whereas chronic infection with S. haematobium can lead to renal disease and bladder cancer.

Opisthorchis spp., Clonorchis sinensis, Fasciola hepatica (liver flukes). Found in Asia, Southeast Asia, Eastern Europe, and countries of the former Soviet Union, liver flukes are contracted by eating undercooked freshwater fish. They inhabit the bile tree of humans, and when they cause disease it results in symptoms of abdominal discomfort, diarrhea, and constipation secondary to bile duct inflammation and biliary obstruction. Chronic infection results in inflammation and scarring of the biliary tree, which can lead to gallbladder and bile duct cancers. In fact, some species may be mistaken for gallstones and only be discovered upon surgery.

Of note, Fasciola, the common liver fluke, is found in a more broad geographical swath and is acquired not by uncooked or undercooked seafood, but by eating raw freshwater plants, such as watercress (as well as undercooked sheep or goat livers) [11]. Symptoms are similar to the other liver flukes, despite this parasite’s actively burrowing through the liver parenchyma to arrive at the biliary tree. The most commonly encountered liver flukes in refugees are Opisthorchis and Clonorchis and are seen mainly in SEA refugees (e.g., Laotian).

Paragonimus westermani (lung fluke). Paragonimiasis is most common in South and Southeast Asia, where humans are infected by eating raw or undercooked crab or crayfish. Symptoms of infection first involve the abdominal tract, with nausea, vomiting, and diarrhea, and may then be followed by pulmonary symptoms including chest pain, fever, and cough which may be productive of bloody sputum [12]. Given the prominence of hemoptysis, tuberculosis is often considered along with paragonimiasis in the differential diagnosis [13]. This infection is seen primarily in SEA refugees, currently most common in Burmese refugees.

Cestodes

Inhabiting the intestines of humans, cestodes have long been regarded with revulsion by man, most probably second to passage in the feces of entire worms of great length (e.g., Diphyllobothrium which can be over 10 ft when excreted) or of gravid proglottids (large, egg-laden segments of the worms), seen primarily with Taenia spp.

Hymenolepis nana (dwarf tapeworm). Found throughout the world, and particularly where there is poor hygiene, this parasite is commonly called the “dwarf tapeworm.” Humans are infected by fecal-contaminated food or water, and most patients are asymptomatic with infection because of the small size of this tapeworm compared to the members of genus Taenia. Symptoms if present are usually of abdominal discomfort and weakness, and children with heavy infections may have perineal pruritus and therefore be misdiagnosed with pinworm infection. This is particularly common in Ethiopian and Somali refugees.

Taenia saginata (beef tapeworm). Found throughout the world, Taenia saginata is the largest tapeworm to cause human disease, reaching lengths of up to 10 m. Humans are infected by eating raw or undercooked beef and when symptomatic will often have abdominal discomfort, weight loss, and anorexia.

Taenia solium (pork tapeworm). The pork tapeworm, like the beef tapeworm, is found throughout the world and causes a similar clinical presentation when it affects the gastrointestinal system. However, unlike the beef tapeworm, Taenia solium eggs can be directly infectious to humans (i.e., there is the possibility of human-to-human infection). When another human is directly infected by eating eggs, the parasite can migrate to any number of different tissues and develop into cysts; the most worrying location is the brain, which results clinically in neurocysticercosis, which is a significant cause of adult onset seizures in many parts of the developing world [14]. In an immigrant, particularly from Central or South America, who presents with new onset seizures, neurocysticercosis must be on the differential.

Diphyllobothrium latum (fish tapeworm). Obtained through eating raw or undercooked fish, diphyllobothriasis is found primarily throughout the northern hemispheres and is more common within the United States than in refugee populations entering the United States. Symptoms, when present, may be vomiting, diarrhea, and weight loss. Of note is the propensity for vitamin B12 deficiency and consequent anemia.

Table 6.6 outlines the therapeutic regimens for the above parasites for adults.

Table 6.6 Adult therapeutic regimens [15]
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All medications are dosed for adults and orally taken unless otherwise noted [15].

More detailed descriptions of organisms discussed above, as well as therapeutic treatment regimens, can be found in these references [2, 11, 13, 15].

Eosinophilia

An elevated eosinophil count may be the result of any number of infectious and noninfectious processes (see Tables 6.7 and 6.8), but in certain groups it can help bring to the fore the possibility of a latent and perhaps asymptomatic, parasitic infection. Unfortunately things are not as straightforward as they may seem; eosinophilia, or an absolute eosinophil count greater than 400/mm3 in a peripheral blood sample, has both poor negative and poor positive predictive values as a marker of parasitosis in returning travelers [16]. However, as with all tests, a thorough history will reveal characteristics that render the above value more or less likely an indicator of parasitic disease. For example, in the case of patients who have had prolonged exposure to possible helminth infections, eosinophilia becomes much more useful as a possible indicator of underlying, chronic infection.

Table 6.7 Causes of eosinophilia (from CDC Domestic Intestinal Parasite Guidelines) [5]
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Table 6.8 Causes of eosinophilia in refugees, by region [5]
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In the previous sections of this chapter, we have detailed the presumptive therapy which newly arrived immigrants should undergo upon arrival to the United States. It is important to recall that an elevated eosinophil count can take some time, from 3 to 6 months, to return to normal after treatment. Therefore, in patients who have been treated, a recheck of the peripheral eosinophil count should be performed 3–6 months afterward to ensure resolution. If the eosinophil count remains elevated, a more detailed work-up should be pursued, with particular emphasis on Strongyloides, soil-transmitted helminths, and Schistosoma species as these are the most common causes. During this work-up, it will as always be important to consider the geographic region from which the patient is coming, as this will be very important to help clarify the differential diagnosis and arrive at the most likely etiology. If 6 months after presumptive treatment the eosinophil count is still elevated, the differential must be broadened to include other infectious and noninfectious causes.

Finally, it should be noted that the duration of infection with parasites that result in an elevated eosinophil count can be very long, indeed with an organism such as Strongyloides it may last the entire life of the patient because of autoinfection. Other parasites with a long duration of infection are Schistosoma (32 years) and Loa loa (16–24 years). Hookworm and Ascaris are examples of parasites with relatively shorter life spans (3–5 years and 1–1.5 years, respectively) [17].

Treatment should be directed at the parasite identified during eosinophilia evaluation. However, despite a thorough investigation, it is quite possible that an etiologic cause may not be identified, in which case presumptive therapy may be reasonable. In this case, single-dose therapy with ivermectin and/or albendazole has been proposed [17].

Conclusion

Parasitic infections continue to be highly prevalent and an important cause of morbidity in newly arrived refugees. A complete history, including geographic risk factors and the screening recommendations outlined above, can help detect a majority of these intestinal parasitic infections. Recommendations on diagnosis and treatment of these infections are periodically updated by CDC and providers are encouraged to access this information for guidance on management.