Presumptive Treatment and Medical Screening for Parasites in Refugees Resettling to the United...

TROPICAL, TRAVEL AND EMERGING INFECTIONS (L CHEN, SECTION EDITOR)

Presumptive Treatment and Medical Screeningfor Parasites in Refugees Resettling to the United States

WilliamM. Stauffer & Paul T. Cantey & SusanMontgomery &

LeAnne Fox & Monica E. Parise & Olga Gorbacheva &

Michelle Weinberg & Annelise Doney & Lisa Rotz &

Martin S. Cetron

Published online: 18 May 2013# Springer Science+Business Media New York (outside the USA) 2013

Abstract More than 50,000 refugees are resettled to theUnited States annually, many from areas highly endemicfor parasites. Some of these infections present little clin-ical consequence after migration, but others are responsi-ble for morbidity and mortality. The Centers for DiseaseControl and Prevention has issued predeparture presump-tive treatment and postarrival medical guidelines for themanagement of parasites. Although these guidelines areevidence based, there remain significant challenges topresumptive treatment programs in refugees. Gaps inthe evidence continue; resettling populations are continu-ally changing, thus altering the epidemiology; and thereare logistical and cost barriers to fully implementingrecommendations. This article will review the evolutionand status of current guidelines, as well as identify gapsand challenges to full implementation. It is imperative for

clinicians serving this population to be familiar with in-terventions received by refugees, since previous treatmentwill impact screening, diagnostic evaluation, and treat-ment decisions.

Keywords Intestinal parasites . Schistosomiasis .

Refugees . Presumptive therapy . Screening .

Strongyloidiasis

Introduction

Human Mobility and the Prevalence of Parasitic Infection

The United Nations High Commissioner for Refugees(UNHCR) estimated that, in 2010, there were 43.7 million

Curr Infect Dis Rep (2013) 15:222–231DOI 10.1007/s11908-013-0331-7

W. M. Stauffer (*)Department of Medicine, Division of Infectious Diseases andInternational Medicine, University of Minnesota, 420 DelawareStreet SE, Mayo Building D407, MMC 250,Minneapolis, MN 55455, USAe-mail: [email protected]

P. T. Cantey : S. Montgomery : L. Fox :M. E. PariseDivision of Parasitic Diseases and Malaria, Center for GlobalHealth, Centers for Disease Control and Prevention, 1600 CliftonRoad, MS A-06,Atlanta, GA 30333, USA

P. T. Canteye-mail: [email protected]

S. Montgomerye-mail: [email protected]

L. Foxe-mail: [email protected]

M. E. Parisee-mail: [email protected]

O. GorbachevaInternational Organization for Migration, Geneva, Switzerlande-mail: [email protected]

O. GorbachevaInternational Organization for Migration, Station Damk, 768/12,Thirbam Sadak, Baluwater-5, PO Box 25503, Kathmandu, Nepal

W. M. Stauffer :M. Weinberg :A. Doney : L. Rotz :M. S. CetronDivision of Global Migration and Quarantine, Centers for DiseaseControl and Prevention, 1600 Clifton Road, MS A-06,Atlanta, GA 30333, USA

M. Weinberge-mail: [email protected]

A. Doneye-mail: [email protected]

L. Rotze-mail: [email protected]

M. S. Cetrone-mail: [email protected]

refugees and internally displaced persons due to events such ascivil conflict and natural disasters [1]. The UNHCR facilitatesdurable solutions for refugees, such as voluntary repatriationand local integration. When these are not options and refugeesare in a particularly vulnerable situation, UNHCR advocatesresettlement to a third country. The United States (U.S.) is thelargest resettlement country, accepting more than 50,000 ofthese refugees annually [2]. Refugee populations are a vulner-able and medically disenfranchised population in both thedeparture and the resettlement countries. Several points ofcontact during the migration process offer opportunities tominimize infectious disease threats to the public health ofresettlement countries, as well as improve the individual refu-gee’s health status through preventive services, diagnostics, andtreatment. Refugee resettlement to the U.S. is organized in away that may serve as a model for how public health systemscan utilize the immigration process to improve the population’shealth during migration. This article addresses the current bestpractices and challenges for management of common parasiticinfections in refugees resettling to the U.S. In addition, ithighlights how points of contact during the migration journeymay be leveraged to provide cost-effective health interventions.

At least one third of the world’s population is infectedwith parasites, making these infections some of the mostcommon health conditions detected in newly arrived refu-gees [3–6]. Although parasitic infections may be asymptom-atic or subclinical, many are associated with substantialmorbidity (e.g., hookworm contributing to anemia). In ad-dition, several organisms have the potential to cause chronicinfection and may lead to serious health consequences,including death (e.g., schistosomiasis, strongyloidiasis).The parasitic infections encountered in refugees reflect theunderlying epidemiology of the parasites in the populationand region where refugees have lived or been exposed.

Prevalence data for parasitic infections in refugee groupscome primarily from refugee screening programs and pub-lished reports of infection in convenience samples of refu-gees; therefore, reported prevalence estimates range widely,from 8 % to 86 % [7]. These divergent prevalence estimatesmay be explained by population differences in geographicorigin, age distribution, living conditions (including qualityof drinking water, sanitation, and access to footwear), die-tary habits, education level, past occupational exposures,and previous countries of asylum. In addition, differencesmay be partially explained by differences in type of testing(e.g., serology vs. stool testing) and methodologic differ-ences in the testing performed to identify infection [8].

Initial Recommendations for Presumptive Treatmentfor Parasites in Refugees Prior to Departure

During the 1980s and 1990s, state and local health depart-ments and the Centers for Disease Control and Prevention

(CDC) observed that intestinal parasites were prevalent inrefugees relocating to the U.S. In 1997, the CDC and theInternational Organization for Migration conducted enhancedscreening for intestinal helminthic and protozoan infections ina group of Somali refugees living in refugee camps in Kenya.They found that 38 % harbored potentially pathogenic intes-tinal parasites [9]. At the time, published cost effectivenessmodeling estimated that if all immigrants and refugees immi-grating to the U.S. were presumptively treated withalbendazole prior to migration, at least 374 hospitalizationsand 33 deaths would be averted annually and substantial costsavings would be realized [10]. In response to the epidemio-logic data and the presumptive treatment model, the CDCissued guidelines in May 1999, recommending presumptivetreatment of all nonpregnant refugees over the age of 2 yearswith a single dose of albendazole within 3 days of departure tothe U.S.

Impact of 1999 Recommendations on Parasitic Infectionson Soil-Transmitted Helminthiasis (Ascaris, Trichuris,and Hookworm Infection)

Soil-transmitted helminths (STHs) are among the most com-mon parasitic infections found in humans. More than 800, 600,and 500 million people are estimated to be infected withAscaris, Trichuris, and hookworm, respectively [3]. AlthoughSTH infections are frequently asymptomatic, they may beassociated with malnutrition, stunting and impaired growth,anemia, and cognitive deficits, as well as syndromes that aremore specific to each organism, such as small bowel obstruc-tion with ascariasis and dysentery or colitis with trichuriasis. Ofthese three most common STHs, hookworm represents thelargest threat to individual and public health. Hookworm infec-tion may result in sustained and sometimes severe anemia inchildren and pregnant women, decreased school attendance andimpaired cognition in children, and reduced wages in adults.

The recommended predeparture single-dose albendazoletreatment has dramatically decreased the prevalence of com-mon STH infections in refugees. A recent evaluation ofmore than 26,000 African and Asian refugees demonstratedthat single-dose albendazole was associated with an abso-lute reduction of positive stool ova and parasite (O&P)examinations from a prerecommendation baseline of 20.8 % to 4.7 %; albendazole-treated refugees were less likelythan untreated refugees to have any nematode detected(prevalence ratio [PR] 0.19; 95 % CI: 0.17–0.22), Ascaris(PR 0.06; 95 % CI: 0.04–0.09), hookworm (PR 0.07; 95 %CI: 0.05–0.09), or Trichuris (PR 0.27; 95 % CI: 0.23–0.32)[11]. These findings are in agreement with those of an earlierstudy of 1,254 African refugees, which found that refugeesarriving after implementation of the program were less likelythan those resettling prior to the program to have infectionwith intestinal helminths (OR 0.15, 95 % CI: 0.09–0.24),

Curr Infect Dis Rep (2013) 15:222–231 223

including hookworm (OR 0.03, 95 % CI: 0.00–0.29),Trichuris (OR 0.05, 95 % CI: 0.02–0.13), and Ascaris (OR0.07, 95 % CI : 0.01–0.58) [12].

Despite the seemingly impressive success of this inter-vention program, the consequences of untreated STH in-fections after migration to a nonendemic area are not welldelineated, so the full clinical benefit of presumptive therapymay be underestimated. In addition, single-dose albendazoleis not an effective treatment for infection with Strongyloidesand nonnematode parasites such as the Schistosoma species.Strongyloides and Schistosoma species are of particularconcern due to their ability to cause chronic infections andtheir potential to cause serious morbidity and mortality.

Strongyloidiasis

As many as 100 million persons worldwide are estimated tobe chronically infected with Strongyloides stercoralis [7].Seroprevalence surveys have found rates in refugeepopulations ranging from 10 % to more than 75 % [13, 14].If the infection is not detected promptly after arrival, theaverage time to diagnosis of strongyloidiasis is longer than5 years [15, 16]. Although frequently subclinical, strongyloi-diasis may cause gastrointestinal or pulmonary symptoms asthe parasite migrates through the body. Individuals who har-bor Strongyloides are at risk of hyperinfection syndrome ifthey become immunosuppressed, particularly if the immuno-suppression is caused by corticosteroids. Hyperinfection syn-drome results in massive migration of the parasite into internalorgans, causing serious morbidity; its fatality rate exceeds50 % [17, 18]. U.S. clinicians are often unfamiliar withstrongyloidiasis infection and risk of hyperinfection syndrome[15]. Clinicians not familiar with strongyloidiasis may placepatients on immunosuppressive therapy (e.g., corticosteroidsfor asthma), resulting in serious iatrogenic harm [15, 18].Since hyperinfection is frequently associated with gram-negative septicemia, it is likely underdiagnosed andunderreported [18]. Strongyloides hyperinfection may occuryears after exposure, with reports of cases occurring >50 yearsafter last known exposure in an endemic area [17, 19]. HTLV-1 coinfection, common in certain areas where refugees origi-nate (e.g., Southeast Asia), is also associated withhyperinfection. Although antecedent administration of corti-costeroids accounts for most reported iatrogenic cases, thereare reports of Strongyloides hyperinfection resulting fromother immunosuppressed states, such as use of chemothera-peutic agents, transplant immunosuppression, and rarely, hu-man immunodeficiency virus (HIV) [17, 18, 20].

Schistosomiasis

Schistosomiasis (also known as bilharzia, especially byAfrican refugees) is highly endemic in parts of Africa and

Asia but can also be found in foci in South America, theCaribbean, and the Middle East. An estimated 700 millionpeople are at risk of infection, with >200 million infected. Insome endemic areas, infection rates surpass 90 % [21, 22].Schistosomiasis can persist in humans for more than30 years, and untreated infection has been associated withmany other diseases, including liver cirrhosis with resultingcomplications such as portal hypertension with Schistosomamansoni and S. japonicum, squamous cell carcinoma of thebladder with S. haematobium, and urinary tract obstruction,infertility, and renal failure with S. haematobium [21]. Po-tentially devastating clinical manifestations occasionally oc-cur when an egg enters the systemic circulation and lodgesin a terminal vessel in an internal organ, causing severeinflammation. Eggs may travel to virtually any part of thebody, including the brain and spinal cord, where they maycause paralysis or myelitis [21].

The epidemiology of schistosomiasis in resettlingpopulations is becoming increasingly defined. Sudaneseand Somali refugees arriving in the U.S. have beenfound to have a schistosomiasis seroprevalence of 46 %and 73 %, respectively [13]. A study of newly arrivedrefugees with eosinophilia and multiple negative stoolO&P examinations found that 22 % of African refugeeshad schistosomiasis [23]. A recent Australian study founda schistosomiasis seroprevalence of 15 % in all EastAfrican refugees [14]. Data on postarrival morbidity andmortality due to schistosomiasis are limited to case re-ports and case series but indicate that disease is ongoingand that misdiagnosis and mismanagement occur [24–28].Since wide-scale migration from sub-Saharan Africa(SSA) to the U.S. is a relatively recent phenomenon,reports of chronic complications of untreated disease areexpected to increase.

Presumptive Treatment and Screening Guidelinesfor Refugees Resettling to the U.S. as of January 1, 2013

Recommendations for Overseas Presumptive Treatmentof Intestinal Parasites for Refugees Destined for the U.S.

In 2005, the CDC recommended adding presumptive treat-ment for strongyloidiasis (ivermectin) for refugees fromAsia, the Middle East, and non-Loa-loa-endemic Africancountries and treatment for schistosomiasis (praziquantel)for refugees from SSA, in addition to the single-dosealbendazole. Single-dose albendazole has limited effective-ness for Trichuris; the addition of ivermectin to the regimenmay increase efficacy against this organism [29, 30], al-though further research is needed. In some neglected tropi-cal disease control programs, praziquantel is given at thesame time as albendazole and ivermectin, but vigilant

224 Curr Infect Dis Rep (2013) 15:222–231

assessment for adverse reactions is required. Current com-plete predeparture parasitic presumptive therapy regimensand dosing for refugees migrating to the U.S. from Africa,Asia, and the Middle East are summarized in Tables 1 and 2.

Precautions and Contraindications to the Useof Presumptive Therapy

Presumptive therapy should not be administered topopulations for whom the safety of the medication hasnot been demonstrated or who have a condition thatincreases the risk of adverse events. Safety of thesemedications has not been clearly documented in youngchildren and pregnant and breastfeeding women. Infor-mation on the use of the recommended antihelminthicsin the populations can be found in the Resources forHealth Professionals section of the CDC disease-specificWeb pages (www.cdc.gov/parasites). In addition, any refugeewith suspected or proven neurocysticercosis or a history ofunexplained seizures should not receive presumptive therapy.Although strongyloidiasis is preferentially treated with iver-mectin, rare cases of fatal encephalopathy have been associatedwith persons who are co-infected with Loa loa. Therefore,refugees from SSA at risk for Loa loa should not receivepresumptive treatment with ivermectin.

For details on dosing, logistics of administration, moni-toring for adverse events, and further information on use inspecial populations, please see details in the full guidelines:

www.cdc.gov/immigrantrefugeehealth/guidelines/overseas/intestinal-parasites-overseas.html (accessed May 21, 2012).

Guidelines for Presumptive Treatment and/or Screeningof Refugees After Arrival to the U.S. as of January 1, 2013

The guidelines for presumptive treatment and medical screen-ing were developed on the basis of the best available evidenceand expert opinion (Box 1). Although the CDC hasrecommended a package of presumptive treatments for STH,Strongyloides (all refugees except sub-Saharan Africans fromloiasis-endemic countries), and Schistosoma (sub-Saharan Af-ricans only) prior to departure, not all refugees are currentlyreceiving the complete package of recommended treatments.Overseas guidelines and implementation of the presumptivetherapies vary over time and are dependent upon cost, avail-ability of medications, and logistical challenges, as well asevolving data and best practices. Thus, postarrival guidelinesare designed to be flexible and are contingent upon whetherthe refugee received the predeparture presumptive treatment.Ideally, the clinician will have documentation of presumptivetherapy received by each refugee at the time of the screeningvisit for new arrivals. However, this documentation is notconsistently available. In cases where the documentation isnot available, presumptive treatment can reasonably be as-sumed to have been received by individual refugees from apopulation where the program is being implemented (link:www.cdc.gov/immigrantrefugeehealth/guidelines/domestic/domestic-guidelines.html) and as long as no contraindicationswere present at the time of departure. The CDC periodicallymonitors ongoing programs and has documented 75–100 %compliance rates in populations that are currently treated.

Box 1. Formulation of the guidelines for presumptive treatmentand/or screening of refugees after arrival to the United States

The guidelines presented in this document represent the first nationalguidance for medical screening for intestinal parasite in refugeesafter arrival to the United States. These guidelines are theculmination of an extensive process based on available evidence-based data, including review of all available data on parasitic in-fections of endemic populations, refugee populations, and immi-grant populations by CDC’s Division of Global Migration andQuarantine and Division of Parasitic Diseases and Malaria. Inaddition, World Health Organization and other international orga-nization recommendations were reviewed to maintain consistencybetween programs where possible. Data on medication cost andanticipated adverse effects were considered. In addition to internalCDC review, the draft guidelines were critically reviewed by mul-tiple health and subject-matter experts throughout the UnitedStates. The guidelines were subsequently reviewed and approvedby a Federal Partners Workgroup, which was convened to reviewthe proposed domestic medical screening guidelines. Thisworkgroup consists of representatives from the Department ofHealth and Human Services, Office of Refugee Resettlement andthe Substance Abuse and Mental Health Services Administration,Department of State, and State Refugee Health Coordinators.

Table 1 World Health Organization praziquantel and ivermectin dos-ing based on height [34]

Height Drug and dosing

Praziquantel1,2

<94 cm Not recommended

94–109 cm 1 tablet (600 mg)

110–124 cm 1-1/2 tablets (900 mg)

125–137 cm 2 tablets (1,200 mg)

138–149 cm 2-1/2 tablets (1,500 mg)

150–159 cm 3 tablets (1,800 mg)

160–177 cm 4 tablets (2,400 mg)

≥178 cm 5 tablets (3,000 mg)

Ivermectin3

<90 cm Not recommended

90–119 cm 1 tablet (3 mg)

120–139 cm 2 tablets (6 mg)

140–159 cm 3 tablets (9 mg)

>159 cm 4 tablets (12 mg)

1Better tolerated if divided into two doses and given 12 h apart2 Using 600-mg Praziquantel tablets3 Using 3-mg Ivermectin tablets


http://www.cdc.gov/parasites

http://www.cdc.gov/immigrantrefugeehealth/guidelines/overseas/intestinal-parasites-overseas.html

http://www.cdc.gov/immigrantrefugeehealth/guidelines/overseas/intestinal-parasites-overseas.html

http://www.cdc.gov/immigrantrefugeehealth/guidelines/domestic/domestic-guidelines.html


Some refugees may receive no overseas treatment, otherswill receive a single dose of albendazole, and still others willreceive a more comprehensive regimen of albendazole forSTH and ivermectin for strongyloidiasis and/or praziquantelfor schistosomiasis. As of July 2012, most eligible refugeesdeparting from the Middle East, Africa and Asia are receiv-ing presumptive single-dose albendazole. Eligible refugeesdeparting from SSA are receiving presumptive praziquantel.Currently Burmese and Bhutanese refugees are receiving thecomplete presumptive treatment package, since they receivepredeparture ivermectin for strongyloidiasis. Predeparturepresumptive treatment for strongyloidiasis may be ex-panded to other U.S.-bound refugees in the near future.

Algorithms have been developed to guide postarrival man-agement of parasitic infections for those who received notherapy (Fig. 1), incomplete presumptive treatment (Fig. 2),and complete presumptive treatment (Fig. 3). The status of

predeparture presumptive treatment in specific populationsresettling to the U.S. is available at the CDC Web site:www.cdc.gov/immigrantrefugeehealth/guidelines/domestic/domestic-guidelines.html (accessed May 21, 2012).

Management of Asymptomatic Refugees for Parasitic InfectionIf They Received No Predeparture Treatment (Fig. 1)

The algorithm in Fig. 1 describes the management of refugeeswho receive no predeparture presumptive treatment. Thisgroup is primarily refugees who are not currently included inpredeparture presumptive treatment programs, either becausesuch treatment was not recommended or because there was acontraindication at the time of treatment (e.g., pregnancy,breast-feeding, too young). These refugees may be either testedfor infection or presumptively treated after arrival, if there is nocontraindication. Refugees who fall into this category need

Table 2 Recommended medication regimen for presumptive treatment of parasitic infections

Refugee population Regimens by pathogen

Soil-transmitted helminths:Albendazole

Strongyloidiasis: Ivermectin orhigh-dose albendazole

Schistosomiasis: Praziquantel

Adults

Asia, Middle East,and North Africa,Latin America andCaribbean

400 mg orally for 1 day Ivermectin, 200 μg/kg/day orallyonce a day for 2 days

Not recommended

Sub-Saharan Africa,non-Loa loa-endemicarea

400 mg orally for 1 day Ivermectin, 200 μg/kg/day oncea day for 2 days

Praziquantel, 40 mg/kg (may bedivided and given in two dosesfor better tolerance).

Sub-Saharan Africa,Loa loa-endemicarea

400 mg orally for 1 day Only use ivermectin (200 μg/kg/dayonce a day for 2 days) if Loa loainfection has been ruled out. Mayuse high-dose albendazole (400 mgtwice a day for 7 days) if Loa loainfection cannot be ruled out.

Praziquantel, 40 mg/kg (may bedivided and given in two dosesfor better tolerance).

Pregnant women

Asia, the MiddleEast/North Africa,Latin America andCaribbean

400 mg orally for 1 day (if in 2ndor 3rd trimester). First trimester,not recommended

Not recommended Not recommended

Sub-Saharan Africa 400 mg orally for 1 day (if in 2ndor 3rd trimester). First trimester,not recommended

Not recommended Praziquantel, 40 mg/kg (may bedivided and given in two dosesfor better tolerance).

Children

Asia, the MiddleEast/North Africa,Latin America andCaribbean

12–23 months of age: 200 mg orallyfor 1 day. Presumptive therapy is notrecommended for any infant lessthan 12 months of age.

Ivermectin, 200 μg/kg/day orallyonce a day for 2 days

Not recommended

Should not be used presumptivelyif ≤15 kg or from Loa loa-endemiccountry.

Sub-Saharan Africa 12–23 months of age: 200 mg orallyfor 1 day. Presumptive therapy is notrecommended for any infant lessthan 12 months of age.

Ivermectin, 200 μg/kg/day orallyonce a day for 2 days

Children ≤4 years of age should notreceive presumptive treatment withpraziquantel. Only for children fromsub-Saharan Africa

Should not be used presumptivelyif ≤15 kg or from Loa loa-endemiccountry.

Note. All sub-Saharan African countries are considered endemic for schistosomiasis except Lesotho




screening or presumptive treatment for soil-transmittedhelminthes and either presumptive treatment for strongyloidi-asis and schistosomiasis, depending on their country of origin,or screening and treatment, if indicated, for the two parasites.

Management of Parasitic Infections in PopulationsCurrently Receiving Parasitic Predeparture PresumptiveAlbendazole But Who Did Not Receive Full PredepartureTreatment (Fig. 2)

Most refugees currently receive albendazole therapy but nottreatment for strongyloidiasis or schistosomiasis, even thoughsuch treatment may be indicated. The algorithm for managingthese refugees is described in Fig. 2. Depending on whichindicated treatment the individual refugee has not received,the clinician will need to select either the appropriate pre-sumptive treatment or a screen-and-treat strategy. The strategyfor strongyloidiasis is complicated by the loiasis issue forthose refugees coming from co-endemic areas in SSA. Pre-sumptive treatment for strongyloidiasis for refugees from non-Loa-loa-endemic countries is two doses of ivermectin givenon 2 consecutive days (Tables 1 and 2). For those from Loa-loa-endemic areas, a screen-and-treat approach is usuallypreferable, although presumptive high-dose, long-coursealbendazole, with or without screening, is an acceptable alter-native for presumptive treatment of Loa loa (Table 2).

Screening for strongyloidiasis should include serologictesting or stool culture. Stool ova and parasite examina-tion may be used, but testing of three samples results inless than 60 % sensitivity. Up to seven samples may benecessary to increase sensitivity to more than 90 %. Se-rologic testing is the most widely available testing modal-ity, and positive results are sufficient to confirm thediagnosis. However, a combination of more than onetesting technique may increase sensitivity and specificity(e.g., serology combined with stool ova and parasite test-ing). For SSA refugees who have lived in areas endemicfor loiasis, screening for loiasis by using a quantitativedaytime blood smear or filariasis/Loa loa serology isnecessary in order to determine the safety of ivermectintherapy. Refugees who are negative may be treated withivermectin; those who are positive may be treated withhigh-dose albendazole. Testing for Loa loa is not neces-sary if persons with strongyloidiasis are receiving high-dose albendazole. A full discussion of loiasis is beyondthe scope of this article; clinicians should consult a trop-ical medicine specialist with expertise in the managementand diagnosis of loiasis. They may also review the CDCParasitic Diseases Web site for additional information(http://www.cdc.gov/parasites/loiasis/index.html).

For SSA refugees who have not received predeparturetherapy for schistosomiasis, postarrival presumptive treatment

Refugees from Asia and Middle East1. Presumptive albendazole OR stool ova and parasites examination x 2 or more1

2. CBC with differential2

3. Presumptive treatment OR screen and treat for strongyloidiasis

Treat positive pathogenic parasites detected4

Re-check total eosinophil count in 3-6months

Further evaluation only if symptomatic

Yes No

Eosinophilia?5

Further evaluation only if symptomatic Further evaluation of etiology of eosinophilia

Eosinophilia?5

Yes No

Refugees from Loa loa-endemic areas of Africa 1. Presumptive albendazole OR stool ova and parasites examination x 2 or more1


3. Screen for strongyloidiasis and treat if no contra- indications3

4. Presumptive treatment OR screen for schistosomiasis

Refugees from non-Loa loa endemic areas of Africa1. Presumptive albendazole OR stool ova and parasites examination x 2 or more1


3. Presumptive treatment OR screen and treat for strongyloidiasis 4. Presumptive treatment OR screen for schistosomiasis

1Sensitivity varies according to parasite (e.g., very sensitive for Ascaris but may need 7 specimens to reliably exclude Strongyloides) and minimum of two specimens are suggested. 2CBC: Complete blood count and differential (not recommended as screening test for parasitic infection but routinely obtained on screening for newly arrived refugees) 3See text for discussion of screening for Loa loa 4See DPDxLaboratory Identification of Parasites of Public Health Concern.iagnostic and management assistance may be obtained by contacting Division of Parasitic Diseases at CDC. 5Eosinophilia= a eosinophil count of >400 per microliter (µL)

Fig. 1 Management of asymptomatic refugees for parasitic infection if they received no pre-departure treatment


http://www.cdc.gov/parasites/loiasis/index.html

with praziquantel (Tables 1 and 2) is acceptable—or screeningand treatment, if indicated. Serologic testing is the most sen-sitive method for screening. Stool ova and parasite testingmay detect infection, although, similar to testing forstrongyloidiasis, sensitivity can be quite low. Combiningserology and stool testing may increase sensitivity andspecificity. In addition, other findings on routine screeningtests may suggest infection; for example, eosinophilia mayindicate strongyloidiasis or schistosomiasis, or hematuria maysuggest schistosomiasis, although these are nonspecificfindings.

Management of Asymptomatic Refugees for ParasiticInfection Who Received Complete Predeparture Therapy(Fig. 3)

The algorithm in Fig. 3 describes the management of refu-gees who have received all predeparture therapy accordingto the 2012 guidelines. This algorithm will become increas-ingly used as ivermectin therapy is expanded beyond theBurmese refugees originating in Thailand.

Before prescribing presumptive treatment, the clinicianshould be familiar with the precautions and contraindications

Middle Eastern, Asian& SE Asian refugees

CBC with differential4

Recheck total eosinophil countin 3-6 months

Further evaluationonly if symptomatic

Yes No

Eosinophilia?6


Further evaluation of etiologyof eosinophilia

Eosinophilia?6

Yes No

Africanrefugees1

Presumptive ivermectin?


PLUSPresumptive therapy with ivermectin

OR screen and treat for Strongyloides2


PLUSScreen for Strongyloides

and Loa and treatStrongyloides if not

contraindicated5

Originating or from Loa loa-endemic area?3

No Yes

Yes No

Presumptive praziquantel?Presumptive treatmentOR screen and treat for

schistosomaisis2

No

Yes

1Sub-Saharan African refugees without a contraindication are currently receiving pre-departure praziquantel for schistosomiasis. (Consider serologicscreening for those with a contraindication at departure; see Figure 2.)2See text for screening strategies3See list 1 of overseas guidelines and map of Loa loa-endemic countries.4CBC: Complete blood count and differential (not recommended as screening test for parasitic infection but routinely obtained for new arrival screening)5See text for discussion of screening for Loa loa6Eosinophilia = an eosinophil count of >400 L.µ

Fig. 2 Management of parasitic infections by refugee population currentlyreceiving parasitic predeparture presumptive albendazole but incompletepredeparture therapy as of March 1, 2013. Most refugees without a

contraindication are currently receiving pre-departure albendazole. Visitthe CDC’s current immunization schedule for US-bound refugees forcurrent status of predeparture presumptive treatment


for each medication described in the overseas parasiterefugee management recommendations (www.cdc.gov/immigrantrefugeehealth/guidelines/overseas/intestinal-parasites-overseas.html#contraind).

Gaps and Challenges

Population-based presumptive treatment is a foreign conceptto most clinicians in the United States. However, in diseasecontrol programs, presumptive therapy is often an efficientapproach when an infection is highly prevalent; screeningtest performance for the targeted infection is suboptimal;known morbidity and mortality are associated with theinfection; and treatment is simple, well tolerated, effica-cious, cost effective, and safe. For specific patient groups,presumptive therapy may also be desirable when cliniciansare not familiar with the conditions, which can delay diag-nosis and initiation of appropriate treatment and put patientsat iatrogenic risk [15, 17, 18].

Many challenges and gaps in knowledge hinder refugeepresumptive treatment programs. Barriers in implementingand maintaining programs include complex logistics andthe need for agreements between governmental andnongovernmental agencies, drug acquisition and distribu-tion, education and training of health providers deliveringcare overseas, delivery of drug to refugees, programoversight and quality assurance, and tracking, includingthe documentation of treatment that accompanies the

refugees to their final destination. In addition, no dedi-cated funding is currently available to implement andsustain these programs, even though resettlement commu-nities would realize cost savings [10, 31].

Gaps in knowledge remain that inhibit optimizing thepresumptive treatment programs. Despite data demonstrat-ing that presumptive treatment for STH and strongyloidiasisis cost saving in migrant populations [10, 31], treatment hasnot been fully implemented. Additional data on the impactof presumptive therapy for strongyloidiasis and schistoso-miasis are needed and could improve acceptance of therecommendation. An optimal system would adjust recom-mendations to specific populations on the basis of real-timemonitoring of epidemiologic measures of parasitic infection,especially since the populations entering the U.S. varytremendously over time. Furthermore, although some masspreventive chemotherapy programs have become wide-spread in resource-poor countries, many questions remainregarding measurement of impact and program evaluation[33]. Some of the same issues are important for refugeepopulations. For example, the true adverse event rate is notknown for refugees who have neurocysticercosis and areinadvertently treated with albendazole or praziquantel, al-though observed adverse events remain rare. Taenia solium,the causative agent of neurocysticercosis, was thought to beunusual in refugees. Evidence of active infection with theadult T. solium tapeworm is generally observed in <1.5 % ofscreening stool samples [32]. However, a recent serosurveyfor cysticercosis showed that several refugee populations had

All refugees


Re-check total eosinophil count in 3-6 months


Yes No

Eosinophilia?2


Further evaluation of etiology of eosinophilia

Eosinophilia?2

Yes No

1Complete blood count and differential (not recommended as screening test for parasitic infection butroutinely obtained on screening for newly arrived immigrants and refugees)2Eosinophilia = a eosinophil count of >400 µL

Fig. 3 Management of parasiticinfection for asymptomaticrefugees who received completepre-departure therapy as ofMarch 1, 2013


http://www.cdc.gov/immigrantrefugeehealth/guidelines/overseas/intestinal-parasites-overseas.html#contraind



high lifetime exposure rates to this important pathogen [33].Further study of the epidemiology of parasitic infections andmeasurement and evaluation of the impact of presumptivetreatment, as well as cost analysis, are needed to optimizepresumptive treatment programs.

Conclusions

Because parasitic infection is common in refugees relocatingto the U.S., the CDC has issued guidelines for presumptivetreatment for the most common and severe parasitic infec-tions affecting refugees, including STH, strongyloidiasis,and schistosomiasis. The recommendations for completepredeparture presumptive treatments are not uniformlyimplemented, and therefore the postarrival guidelines are con-tingent upon therapy received prior to departure. Despitechallenges, predeparture presumptive therapy has been shownto be effective. This approach of addressing infection anddisease during the migration process may represent a modelof how to leverage points of contact to improve individualhealth and promote successful integration into resettlementcommunities.

Acknowledgments We extend our gratitude to Drew Posey for hisearly work and thoughts on this project.

Conflict of Interest Statement William M. Stauffer declares that hehas no conflict of interest.

Paul T. Cantey declares that he has no conflict of interest.Susan Montgomery declares that she has no conflict of interest.LeAnne Fox declares that she has no conflict of interest.Monica E. Parise declares that she has no conflict of interest.Olga Gorbacheva declares that she has no conflict of interest.Michelle Weinberg declares that she has no conflict of interest.Annelise Doney declares that she has no conflict of interest.Lisa Rotz declares that she has no conflict of interest.Martin S. Cetron declares that he has no conflict of interest.

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