Eosinophilia in Travelers: A Role for Empiric Antihelminthic Therapy?
Abstract & Commentary
By Brian G. Blackburn, MD, Clinical Assistant Professor of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine
Synopsis: A retrospective review of ill returned travelers in Israel revealed that almost 9% had eosinophilia. Although half with eosinophilia were diagnosed with schistosomiasis, a confirmed parasitologic diagnosis was rare in the remainder. Empiric albendazole therapy led to clinical improvement in 90% of patients with non-schistosomal eosinophilia.
Source: Meltzer E, et. al. Eosinophilia among returning travelers: a practical approach. Am J Trop Med Hyg. 2008; 78:702-709.
Ill travelers returning from the developing world represent a unique patient population, given the broad range of possible diagnoses. Eosinophilia is thought to be a relatively common finding in this group, and although many medical conditions cause eosinophilia, infectious etiologies are more likely in such patients. Despite the knowledge that helminths are the infectious agents responsible for the majority of such cases, a microbiologic diagnosis remains elusive in many patients with eosinophilia.
Meltzer and colleagues undertook a retrospective review of travelers to the developing world that presented (after returning home) to a medical center in Israel. The study spanned a 12-year period, and immigrants from developing countries were excluded. Patients presented a median of 6 weeks after returning from travel. Of the 955 patients reviewed, 82 (9%) had eosinophilia (> 500 eosinophils/µL or > 6% of the total white blood count). Forty-four (54% of those with eosinophilia) of these were diagnosed with schistosomiasis. Although all were seropositive, Schistosoma ova were found in the stool or urine in only 23% of those tested. Thirty-eight (46%) patients had non-schistosomal eosinophilia (NSE), and a parasitological diagnosis was confirmed in only 24% of these persons. Although patients with NSE did not undergo uniform evaluation, of the 30 who submitted at least one stool sample for ova and parasite examination, 3 (10%) were positive for helminths (hookworm in three; one coinfected with Ascaris). One additional patient had hookworm in a sputum sample. Of the 11 tested serologically for Strongyloides, 5 (45%) were positive. Although protozoa were found in 4 patients, these organisms were not considered explanatory of eosinophilia.
Of the 38 patients with NSE, 36 (95%) were symptomatic; most had gastrointestinal symptoms, and many had dermatologic and respiratory symptoms. The median eosinophil count among these patients at presentation was 1700 cells/µL. Of the 30 patients treated empirically with albendazole (most commonly 400 mg twice per day for 5 days) that had follow-up information available, symptoms subsequently resolved in 77% and improved in 13%, with no response in only 10%. The median eosinophil count decreased to 400 cells/µL among the treated NSE patients. In addition, patients diagnosed with schistosomiasis were treated with praziquantel.
Commentary
This study demonstrates the relative frequency with which ill travelers returning from the developing world present with eosinophilia. Previous work focusing on refugees has demonstrated similar findings,1 but less data are available on non-immigrant travelers. Also notable is the frequency of schistosomiasis in travelers with eosinophilia, particularly when there is a history of travel to Africa (95% of patients with schistosomiasis-associated eosinophilia in the study had traveled to Africa). Ill-returned travelers from endemic areas with eosinophilia should be tested for schistosomiasis, probably both by serology and direct examination of stool or urine; if positive, treatment with praziquantel will cure most patients.2 In patients with non-schistosomal eosinophilia, establishing a parasitological diagnosis is difficult given that stool ova and parasite examinations are insensitive for many helminths and serological testing suboptimal.
Given the increased likelihood of helminthic infection and the difficulty of establishing a diagnosis in this population, empiric albendazole is an attractive strategy in returned travelers with NSE. Empiric albendazole has been shown to significantly decrease the prevalence of intestinal helminths in refugees resettling to the United States,3,4 but evaluation in travelers is less established. The current study demonstrated clinical improvement and decreased eosinophil counts in almost all patients with NSE who were treated with albendazole. Although limited by the retrospective nature of the study, this suggests a helminthic cause in most of these patients, even though few had a confirmed parasitological diagnosis. Of particular importance is the issue of strongyloidiasis, given the lifelong nature of untreated infection and subsequent possibility of the fatal hyperinfection syndrome in certain hosts. Although the antiparasitic regimen used in this study is a second-line option for Strongyloides stercoralis, it has been shown to cure many patients.5 Treatment directed at this parasite has also previously been shown to decrease eosinophil counts within months of treatment,6 and given the high strongyloidiasis prevalence among tested persons in this study, suggests that many of the patients with NSE were responding to treatment for S. stercoralis. Although Meltzer et al also raise the issue of testing and possible treatment of filariasis, exposure history should be considered heavily when considering this diagnosis in casual travelers, given the relative rarity in this population.7 .Overall, it seems reasonable to screen ill-returned travelers as appropriate for eosinophilia, and proceed with a rational workup, including schistosomiasis testing, if the patient has traveled to an endemic area, stool ova and parasite examination, and serologic testing for strongyloidiasis. If negative, and no other diagnosis is suggested, these data suggest that empiric albendazole followed by clinical and laboratory reassessment might be a reasonable initial strategy in this patient population.
References
- Seybolt LM, et. al. Diagnostic evaluation of newly arrived asymptomatic refugees with eosinophilia. Clin Infect Dis. 2006;42:363-267.
- Gryseels B. Human schistosomiasis. Lancet. 2006;368:1106-1118.
- Miller JM, et al. Malaria, intestinal parasites, and schistosomiasis among Barawan Somali refugees resettling to the United States: a strategy to reduce morbidity and decrease the risk of imported infections. Am. J Trop Med Hyg. 2000;62:115-121.
- Geltman PL, et. al. Intestinal parasites among African refugees resettled in Massachusetts and the impact of an overseas pre-departure treatment program. Am J Trop Med Hyg. 2003;69:657-662.
- Segarra-Newnham M. Manifestations, diagnosis, and treatment of Strongyloides stercoralis infection. Ann Pharmacother. 2007;41:1992-2001.
- Loutfy MR, et al. Serology and eosinophil count in the diagnosis and management of strongyloidiasis in a non-endemic area. Am J Trop Med Hyg. 2002;66:749-752.
- Addiss D. Lymphatic filariasis chapter. In: Arguin PM, et al, eds. (Centers for Disease Control and Prevention). Health Information for International Travel 2008. Atlanta: Mosby Elsevier (US Department of Health and Human Services, Public Health Service). 2007:147-149.
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