What is eosinophilia and what does it mean?
Eosinophils are a type of myeloid granulocytic cell (white blood cell). The term “eosinophilia” is a clinical term that indicates an elevated peripheral (circulating) eosinophil count or percentage. The definition of “elevated” is considered an absolute peripheral eosinophil count exceeding 400-600 cells per microliter.  This absolute eosinophil count (AEC) is preferred over percentile because an AEC may be elevated even when the percentage of eosinophils is reported as normal. If laboratory test results only show the percentage of eosinophils, the AEC can be calculated by multiplying the total white blood count by the percentage of eosinophils.

An elevated AEC may be primary type (e.g. due to clonal expansion such as with leukemia) or secondary type.  Secondary eosinophilia occurs when eosinophils are mobilized into the peripheral blood as a reaction to defend against an antigen (usually a protein) that is considered foreign by the body’s immune system.  The most common causes of an elevated AEC are allergens and infections, particularly parasitic infections.  However, please bear in mind that the differential diagnosis of secondary eosinophilia is quite extensive.  See Table 1: Causes of Eosinophilia.

Refugees and eosinophilia
Most refugee health experts consider an eosinophil count exceeding 400 cells per microliter as elevated.  The lower threshold is used because it will increase the sensitivity of the test as refugees have high probability of parasitic infection.

The most common parasitic infections associated with eosinophilia in refugees are the soil-transmitted helminths (trichuris, ascaris and hookworm), strongyloides, and schistosoma as well as many tissue-invasive parasites (e.g. parasites that migrate through human tissues as a part of their life cycle).  Elevated AEC found in refugees is most likely associated with a tissue-invasive parasite.  More information on intestinal parasites can be found at the CDC Division of Parasitology website as well as in the CDC domestic refugee health guidelines.

While the presence of an increased AEC in a refugee is highly suggestive of current or recent infection with a tissue-invasive parasite, the absence of eosinophilia does not indicate lack of parasitic infection [1, 2]. Not all parasitic infections cause eosinophilia. For example, the human host does not always mount an eosinophilic response to tissue-invasive parasites.  Non-tissue invasive parasites such as protozoa (e.g. giardia and ameba) do not normally illicit an eosinophilic response.

Additionally, many of the tissue-invasive parasites reside in the bowel and only migrate through tissues inciting eosinophilia during specific periods of their life cycle. Further, eosinophilia tends to decrease in persons with chronic infection as the host adjusts to the presence of parasites.  The negative-predictive value of a normal eosinophil count is low for common parasites (e.g. strongyloides, hookworm).  As a result, a normal eosinophil count does not necessarily rule-out a parasitic infection.

Screening for AEC and Treatment
The initial evaluation of elevated AEC in a newly arrived refugee is complicated by pre-departure presumptive parasitic treatment. This is because many of the common parasites that elicit an increased AEC are often treated prior to arrival in the US. Since most refugees are seen within weeks of arrival, it may take several months for an elevated AEC to normalize after presumptive treatment.  Many refugees who are found to have elevated eosinophil count during their domestic health assessment would have already received presumptive treatment for the eosinophilia-inciting organism before arrival in the US [1].  Therefore, the CDC recommends initial evaluation of an increased AEC based on previous anti-parasitic presumptive treatment received:

• Refugees who received the complete presumptive treatment package* should have their eosinophil count repeated in 3-6 months, as it can take this long for eosinophilia to resolve after appropriate treatment.  No further testing is indicated for asymptomatic refugees.
• If the refugee has not received the complete presumptive treatment package,* it is reasonable to provide the missing components of the complete treatment package and recheck eosinophil counts 3-6 months after receiving treatment and prior to embarking on a diagnostic work-up.
• If the refugee has not received the complete presumptive treatment package* and the clinician opts for screening for parasitic infections in lieu of presumptive treatment, the evaluation suggested in Figure 2 or Figure 3 of the CDC guidelines should be followed.

* Complete presumptive treatment package includes treatment for soil-transmitted helminths (single-dose albendazole) PLUS treatment for strongyloidiasis (either ivermectin or high-dose albendazole) PLUS, for sub-Saharan African refugees, treatment for schistosomiasis (praziquantel). Information on current pre-departure regimens being received by specific refugee populations is available from the CDC. 

When an elevated AEC does not resolve with preemptive or directed treatment, a thorough evaluation should be conducted.  Since presumptive treatment is not completely effective initially for common parasites, re-evaluation for common soil-transmitted helminths, strongyloides, and when appropriate, schistosomiasis should be the initial evaluation [1, 2, 3].  Other common parasitic causes of persistent eosinophilia are highly dependent on risk factors such as geographic region and exposure history (e.g. diet). Schistosomiasis and filariasis infections are particularly common in African refugees. Tapeworm infection is found in approximately 2% of refugees overall, and infection from other flukes (e.g. Ophistorochiasis, paragonimiasis) are predominantly found in Southeast Asian refugees [1].

When a common pathogen or other etiology is not identified, a referral to an infectious disease specialist with experience in tropical medicine may be necessary. Steroids or other immunomodulaters sometimes used to treat eosinophilia in the US-born population should be avoided until a thorough evaluation has definitively ruled-out a tissue-invasive parasite, particularly Strongyloides.

Table 1: Causes of Eosinophilia

Parasites	Angiostrongylus cantonesis and A. costaricensis Anisakiasis Ascaris lumbricoides (invasive larval stage) Capillaria phillippinensis Echinococcus Fasciolopsis buski Filariasis Animal hookworms Hookworms (invasive larval stage) Liver flukes Paragonimus westermani Schistosomiasis Strongyloides stercoralis (initial inf. and autoinf.) Toxocara species Trichinosis Tropical eosinophilia (Unidentified microfilariae)
Other infections/ infestations	Pulmonary aspergillosis Severe scabies
Allergic/atopic disorders	Asthma Hay fever Drug reactions Eosinophilic myalgia syndrome-tryptophan, toxic oil syndrome Atopic dermatitis
Autoimmune and related disorders	Hypereosinophilia syndrome (unknown etiology) Polyarteritis nodosa Necrotizing fasciitis Eosinophilic vasculitis Pemphigus Mucin-secreting adenocarcinomas
Immunodeficiency states	Hyperimmunoglobulin E with recurrent infection Wiscott-Aldrich syndrome
Neoplastic diseases	Hodgkin’s disease Mycosis fungoides Chronic myelocytic leukemia Eosinophilic leukemia Polycythemia vera
Other	Addison’s disease Inflammatory bowel disease Dermatitis herpetiformis Toxic/chemical syndrome

Contributed by William Stauffer M.D., M.S.P.H., University of Minnesota

References
1.  Seybolt LM, Christiansen D, Barnett ED.  Diagnostic evaluation of newly arrived asymptomatic refugees with eosinophilia.  Clin Infect Dis. 2006:42(3):363-7.
2.  Goswami ND, Shah JJ, Corey GR, Stout JE. Persistent eosinophilia and Strongyloides infection in Montagnard refugees after presumptive albendazole therapy. Am J Trop Med Hyg 2009;81(2):302-4.
3.  Horton J. Albendazole: a review of anthelmintic efficacy and safety in humans. Parasitology 2000;121 Suppl:S113-32.