Author(s): Michael Libman, Sapha Barkati

Except for coronavirus disease 2019 (COVID-19), CDC has no official guidance or recommendations for screening asymptomatic international travelers in the absence of specific risk factors for infectious diseases. Nevertheless, screening travelers returning from developing countries represents a substantial portion of the activity of many travel health and tropical medicine clinics.

The scientific literature on the clinical utility and cost effectiveness of screening asymptomatic travelers is sparse. Asymptomatic travelers can harbor many infections acquired during travel, some of which have the potential to cause serious sequelae or have public health implications. In some cases, these will include pathogens rarely found in the traveler’s country of origin. US medical practitioners might have little familiarity with these travel-associated diseases, and specific diagnostic tests might not be readily available or will require expertise in their proper interpretation.

Deciding to Screen

The decision to screen an asymptomatic person for travel-acquired pathogens depends on their exposure history, itinerary, type of travel, and the public health implications of identifying infection. Screening healthy short-term travelers for infectious diseases other than COVID-19, especially people who do not report a particular exposure, is usually not necessary. On the other hand, consider obtaining specific tests for long-term travelers (e.g., adventure travelers, expatriates, humanitarian aid workers, missionaries, travelers visiting friends and relatives) who might have prolonged or heavy exposure to epidemiologically relevant pathogens with potential for long-term consequences. A traveler’s exposure history might be unreliable or not predictive of infection, however, and the value of a detailed itinerary can be limited by incomplete information. Finally, the type of travel might not provide a practical assessment of risk.

For the long-term traveler on hiatus from a continuing assignment abroad, the periodic travel health consultation offers the clinician a chance to screen for infectious diseases, conduct a general health evaluation, and to review health behaviors, malaria prophylaxis, and vaccination status. Promote and reinforce primary prevention by discussing behavioral or other risk factors that could predispose the traveler to ill health (e.g., exposures to contaminated food and drink, arthropods, and freshwater sources; drug use; high-risk sex). The usual recommendations for a periodic health exam, which might include screening for cardiovascular disorders, diabetes, hypertension, and malignancy, also apply.

Benefit & Risk of Screening Asymptomatic Travelers

Before scheduling screening tests for asymptomatic returned travelers, evaluate the sensitivity and specificity of the test, and the risk and cost to the patient. The low prevalence of tropical infections in asymptomatic travelers will heavily influence the positive predictive value of the screening tests, leading to an increased likelihood of false-positive results. As a result, the asymptomatic traveler could be subjected to further investigations, generating greater costs, anxiety, and other possible harms related to diagnostic follow-up, creating complex considerations of benefit versus risk.

Screening traditionally has been viewed as a secondary prevention intervention, that is, an attempt to identify occult illnesses or health risks. Cost effectiveness of screening depends on the disease of interest, potential outcomes associated with the disease both for the individual traveler and the public’s health, and whether an early intervention could reduce morbidity or mortality. One exception regarding asymptomatic screening is newly arrived immigrants and refugees; for recommendations regarding these individuals see Sec. 11, Ch. 11, Newly Arrived Immigrants, Refugees & Other Migrants.

Screening For Nonparasitic Infections

Arboviruses

Chikungunya & Dengue

Screening for chikungunya and dengue in asymptomatic travelers typically is not recommended because there are no specific treatments for infection once identified. Travelers concerned about the risk for complications after a secondary dengue infection sometimes request screening. The absolute risk elevation is minimal, however, and generally there is no specific intervention. The exception are children 9–16 years old living in dengue-endemic areas; Dengvaxia vaccine is a prevention option for those presenting with laboratory-confirmed previous dengue infection (see Sec. 5, Part 2, Ch. 4, Dengue).

Zika

The prevalence of Zika virus infection in many countries has decreased dramatically since 2017; as a result, the likelihood of a false-positive test result has increased. Moreover, Zika virus IgM antibody persists months after infection, making it difficult to determine the date of infection, which is crucial information for judging the risk in a pregnant person. Nonetheless, remain vigilant for the potential reemergence of Zika, and review screening guidelines for travelers, including pregnant people and their partners (see Sec. 5, Part 2, Ch. 27, Zika, and CDC's Zika website).

Coronavirus Disease 2019

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has had vast health, social, and economic effects. The emergence of variants makes the evolution of this pandemic unpredictable. As the pandemic progresses, guidance for populations and travelers evolve, as do requirements and recommendations for crossing international borders. For patients who test positive for SARS-CoV-2 after international travel, consider prioritizing specimens for whole genome sequencing, as applicable.

Sexually Transmitted Infections & Bloodborne Pathogens

High rates of sexual activity with new partners, including sex workers, have been documented in overseas backpackers, military personnel, expatriate workers, and people doing volunteer work. Of concern are the low rates of reported condom use. Moreover, travelers might engage in other high-risk activities (e.g., getting a tattoo or piercing, using injection or intranasal drugs, receiving medical or dental care). Returning travelers with acute hepatitis B, hepatitis C, HIV, monkeypox, or syphilis infection pose public health risks and might be hesitant to volunteer a relevant exposure history.

A detailed questionnaire on risk factors for sexually transmitted infections and bloodborne pathogens is recommended for all travelers; always consider screening according to published guidelines. Screening people with relevant exposures should include HIV and syphilis serologic tests, and nucleic acid amplification testing for chlamydia and gonorrhea in urine and at sites of contact (e.g., pharynx, rectum). For travelers with an identified specific risk factor (e.g., blood exposure, condomless sex) who have not been previously vaccinated against hepatitis B virus (HBV), perform HBV testing; hepatitis C virus (HCV) testing also is indicated. Test all travelers born between 1945 and 1965 for HCV if not previously tested.

Tuberculosis

The incidence of tuberculosis (TB) infection related to travel is difficult to estimate. Those with a history of work in high-prevalence settings (e.g., health care institutions, refugee camps) merit screening. Pretravel and posttravel tuberculin skin testing (TST) can require as many as 4 visits to a health care provider—2 pretravel visits for a 2-step test, and 2 posttravel visits after potential exposure. The TB screening process can be simplified by using the interferon-γ release assay (IGRA), which is more expensive but less likely to yield false-positive results in people who received a previous bacillus Calmette-Guérin (BCG) vaccination.

Studies assessing IGRA use for serial testing demonstrated large variations in the rate of conversion and reversion. Fully investigate any positive TST or IGRA result, assess symptoms suggestive of active TB disease, and obtain a chest x-ray. For more information, see Sec. 5, Part 1, Ch. 23, . . . perspectives: Testing Travelers for Mycobacterium tuberculosis Infection.

Screening For Parasitic Infections

Travelers often are most concerned about the possibility of an occult parasitic infection (see also Sec. 11, Ch. 9,. . . perspectives: Delusional Parasitosis). Unfortunately, the literature shows that patient questionnaires and common laboratory testing used to screen for parasitic diseases have poor sensitivity and specificity. Studies have shown that even an exhaustive risk-factor history in asymptomatic patients is unable to reliably detect those who would or would not have evidence of parasitic infection. Physical examination is equally unrevealing.

Most commonly, a stool examination is performed, typically microscopy. Several molecular assays are commercially available to detect a panel of bacterial, viral, and parasitic pathogens. In some cases, these panels are more sensitive than traditional testing methods, and even asymptomatic people often are found to harbor pathogens. The clinical implications of asymptomatic carriage, sometimes at a low level, are unknown for most of these agents, and the risks and benefits of treatment are not well studied. Serologic tests typically are more sensitive for parasitic infections; some have performance limitations related to specificity, but are often preferred for screening asymptomatic travelers.

For questions about parasites and screening for parasitic infections, see the CDC parasites website or contact the CDC.

Helminths

Travelers often are concerned about “worms,” by which they usually mean intestinal helminths (see Sec. 5, Part 3, Ch. 13, Soil-Transmitted Helminths). Infections of travelers with large burdens of the common nematodes (e.g., Ascaris, hookworm, Trichuris) are rare, however. Questioning returning expatriates infected with intestinal helminths has disclosed no attributable symptoms compared with uninfected controls. The life cycles of almost all helminths preclude any real risk of ongoing person-to-person transmission from asymptomatic hosts in high-income countries; helminths generally have a natural lifespan of months to a few years, which ensures eventual spontaneous clearance. In addition, low-intensity infections are of limited clinical importance, though in rare cases aberrant migration of Ascaris spp. can result in clinical disease. The exception to this is Strongyloides stercoralis.

Strongyloidiasis

For Strongyloides infections, serious complications are well known, nonspecific symptoms can easily be overlooked, duration of carriage after infection is unlimited due to its autoinfection cycle, and the original burden of infection is irrelevant (see Sec. 5, Part 3, Ch. 21, Strongyloidiasis). Specific types of immune suppression (e.g., corticosteroid therapy, hematologic malignancy, hematopoietic stem cell transplant, human T-lymphotropic virus type 1 [HTLV-1] infection, solid organ transplant) are risk factors for developing a potentially lethal hyperinfection syndrome or disseminated strongyloidiasis. The COVID-19 pandemic has prompted widespread, urgent dexamethasone use, which could lead to an increased risk for severe strongyloidiasis in exposed travelers and migrants.

Consider screening for strongyloidiasis in select high-risk travelers with potential skin exposure to human feces, usually a result of walking barefoot in areas without proper sanitation facilities. Unfortunately, the sensitivity of stool-based biomolecular and parasitological methods is low. Molecular detection of helminths is more sensitive and specific compared to microscopy, but sensitivity is still insufficient for screening purposes. Moreover, molecular techniques are not widely available outside the reference laboratory and research setting. Serologic methods are often required, as discussed elsewhere in this chapter.

Schistosomiasis

There is no evidence to demonstrate that the low-burden Schistosoma infections typically found in travelers lead to the types of complications found in endemic areas (e.g., liver fibrosis, malignancy). Nevertheless, the possibility of complications cannot be entirely ruled out, particularly in people who have more intense exposures (see Sec. 5, Part 3, Ch. 20, Schistosomiasis). Even brief exposures to freshwater lakes and rivers in known endemic areas in Africa are associated with substantial seroconversion rates. In addition, complications due to ectopic egg migration occasionally can occur in light infections and without warning.

Consider serologic screening in asymptomatic travelers who bathed or swam in freshwater canals, lakes, or rivers in areas endemic for schistosomiasis. Other types of fresh water (e.g., adequately chlorinated swimming pools) carry minimal exposure risk because they do not support the larval parasitic forms. Screening becomes most sensitive only 8–10 weeks after potential exposure and is useful only in those who have not been infected with a schistosome previously. Schistosoma antigens (e.g., circulating anodic antigen [CAA]) can be detected in blood and urine in active infection and can be used to monitor cure after treatment, but sensitivity in asymptomatic travelers is not well studied, and these tests are not widely available.

Interpreting traditional tests for the parasites that cause schistosomiasis and strongyloidiasis can be challenging. Urine and stool examination for Schistosoma spp. and stool examination for Strongyloides lack sensitivity, particularly in low-burden infection; thus, serologic testing has been advocated as the best screening tool. Problems inherent to serologic screening include expense, lack of easy availability, and lack of standardization. Serologic tests often are designed to maximize sensitivity, typically at the expense of specificity. Unfortunately, specificity is almost impossible to define. Seropositivity in the absence of direct pathogen detection is common, and its clinical significance can be difficult to determine.

Fortunately for patients with schistosomiasis (or strongyloidiasis), treatment is easy and effective; for people deemed at risk of strongyloidiasis who require immediate immunosuppression, consider empiric treatment. The common antihelminthic agents used for short-course therapy (e.g., albendazole, ivermectin, praziquantel) have excellent safety profiles. Be aware, however, that rare but severe adverse events can occur when using certain antihelminthics in patients who have occult, unsuspected co-infection with other parasites. Of note, albendazole can cause increased intracranial pressure with focal signs, seizures, and retinal damage in people infected with Taenia solium; diethylcarbamazine can provoke ocular damage in people infected with Onchocerca; and ivermectin can cause encephalopathy in people infected with Loa loa.

Filariasis

Reports of travelers with late complications from asymptomatic filarial infections are virtually nonexistent, and filarial screening (blood or skin snips for microfilaria) is generally not recommended for asymptomatic travelers.

Other Helminthic Infections

Helminth parasitic infections rarely seen in returning travelers include fascioliasis, neurocysticercosis, and paragonimiasis, among others. Screening asymptomatic travelers for these infections is generally not appropriate. Primary care providers should refer patients to an infectious disease specialist when biological, clinical, or radiologic abnormalities increase suspicion for these infections. Intestinal helminths (e.g., Ascaris, Enterobius, hookworms, Strongyloides, Trichuris) rarely cause severe illness in travelers. Other than for Strongyloides in select high-risk travelers, screening is not recommended for intestinal helminth infections.

Protozoa

Blood- & Tissue-Dwelling

Malaria

No justification can be made for screening most asymptomatic travelers for malaria, whether by blood film, molecular methods, or serologic tests. No available tests can detect the latent hepatic forms (hypnozoites) of Plasmodium vivax or P. ovale. Remind travelers to seek evaluation for unexplained fever and to notify practitioners of international travel within the past 12 months.

Immigrants with frequent and regular exposure to malaria might gradually develop partial immunity, which can result in low-level parasitemia with minimal symptoms. Immigrants from malaria-endemic areas might later recrudesce with more severe illness, but this phenomenon is rare in non-immigrant travelers. Of note, in rare cases, travelers compliant with prophylaxis might still acquire malaria; often they will present with low parasitemia infections, and their symptoms can manifest after ending prophylaxis. In these cases, testing asymptomatic travelers is generally inadequately sensitive and not recommended. Rather, advise travelers to remain vigilant for symptoms, particularly unexplained fever.

Trypanosomiasis

Occult trypanosomiasis in asymptomatic travelers (as opposed to immigrants) appears to be extremely rare. Screening tests (e.g., molecular diagnostics, serology) are of unknown value. Consider Trypanosoma cruzi testing for travelers who lived for >6 months in rustic housing (e.g., shelters with mud walls and thatched roofs) in endemic areas of Latin America, especially if they report having seen triatomine bugs inside their dwelling. Also consider testing in people who received blood products in an endemic area, or in travelers with clinical manifestations compatible with acute Chagas disease (see Sec. 5, Part 3, Ch. 25, American Trypanosomiasis / Chagas Disease).

East African trypanosomiasis has affected travelers but typically causes acute symptoms. West African trypanosomiasis generally is not reported in travelers. Refer patients to an infectious disease specialist when these infections are suspected based on biological, clinical, or radiologic abnormalities.

Intestinal

Treat symptomatic intestinal protozoa infections, particularly Entamoeba histolytica which can cause severe disease and ectopic infections (e.g., liver abscess). Except for E. histolytica infection (which is only rarely asymptomatic), the finding of pathogenic protozoa in asymptomatic patients is of questionable significance.

The most common protozoa found in asymptomatic travelers are Blastocystis and Giardia species. History of exposure to contaminated food or water has poor predictive value. No evidence suggests that asymptomatic carriers are likely to develop symptoms later, and the medications used to treat these protozoa can have adverse effects. In theory, asymptomatic carriers pose a public health risk, but transmission by asymptomatic travelers appears to be rare. In addition, stool microscopy for protozoa is expensive, not very sensitive, not highly reproducible, and many laboratories have limited expertise; thus, screening is not recommended unless evidence of onward transmission is present.

Microscopy cannot distinguish Entamoeba histolytica from E. dispar. Differentiation requires further specimen collection and testing. Studies reveal that most travelers with Entamoeba on microscopy are carrying E. dispar. Antigen testing for E. histolytica and Giardia (among others) is fairly reliable but lacks the potential to screen for all intestinal parasites with a single test, and only some antigen tests are able to differentiate E. histolytica from E. dispar.

Commercial molecular methods to screen stool specimens for multiple pathogens simultaneously typically include several protozoa, generally with better sensitivity than microscopy. These assays also can specifically distinguish potentially pathogenic E. histolytica from nonpathogenic amoebae. They offer rapid turnaround times and, although costs remain high, these assays are increasingly being used in returned travelers with suspected protozoal infections. Some of these panels detect organisms for which pathogenicity remains controversial, (e.g., Blastocystis and Dientamoeba). Identifying these pathogens can lead to patient anxiety and unnecessary treatment; thus, screening asymptomatic travelers for intestinal protozoa is not routinely recommended.

General Guidelines

Eosinophilia

Screening for eosinophilia is a common test because it is quick, universally available, and theoretically of value in detecting invasive helminths, if not protozoa. Multiple studies have shown, however, that testing for eosinophilia has poor sensitivity for identifying parasitic infections; the low prevalence of infection in asymptomatic travelers means that the positive predictive value is poor, and the finding of eosinophilia can lead to an extensive and often fruitless search for a cause, generating patient anxiety and high costs. Many cases of eosinophilia resolve spontaneously, possibly because of infection with nonpathogenic organisms or a noninfectious cause (e.g., allergy, drug reaction). Repeat eosinophil counts after several weeks or months before embarking on an extensive investigation.

A recent study in travelers and migrants showed that those with helminthic infection (as compared to other diagnoses) had much higher eosinophil counts. Counts can be highly variable, though, even within a single day, and are suppressed by endogenous or exogenous steroids. Using absolute eosinophil counts, rather than eosinophils as a percentage of leukocytes, is more reproducible and predictive.

Duration of Travel & Other Risk Factors

Table 11-08 and the following traveler classification scheme provide general guidelines for screening asymptomatic returned travelers for imported infections.

All Travelers

See guidance regarding international travel and posttravel COVID-19 testing.

Short-Term Travelers

Screening asymptomatic short-term (<3–6 months) travelers is usually low-yield and should be directed by specific risk factors revealed in the history. A history of prolonged (>2 weeks) digestive symptoms during travel can suggest protozoal infection. Consider serologic testing of travelers who bathed or swam in unchlorinated freshwater sources in regions with known schistosomiasis risk, especially sub-Saharan Africa.

In addition, consider serology testing for Strongyloides in select high-risk travelers who have skin exposure to soil likely to be contaminated with human feces, usually individuals with a history of frequently walking barefoot outdoors. Obtain a sexual history; screen for sexually transmitted and bloodborne infections, if warranted. Zika virus testing for asymptomatic travelers (including pregnant people) with potential exposure is generally not recommended (see Sec. 5, Part 2, Ch 27, Zika). Consider TB screening for those returning from work in health care or other high-risk settings.

Long-Term Travelers & Expatriates

The overall yield of screening increases for longer-stay (>3–6 months) travelers. The emphasis should be on those with the longest stays and the most problematic sanitary conditions or other exposures. In some cases, employers require certain tests, partly for liability reasons. Performing stool examinations mostly provides psychological reassurance. Consider obtaining serologic testing for schistosomiasis and strongyloidiasis in people with recent or remote travel histories to endemic areas and who report some level of risk.

A complete blood count with white blood cell differential and eosinophil counts, liver transaminases, creatinine, and C-reactive protein are usually the basic set of tests performed. Interpret results cautiously; abnormalities might trigger further testing. Zika virus testing for asymptomatic travelers with potential exposure, including pregnant people, is generally not recommended outside of a recognized outbreak. Limit TST or IGRA testing to travelers who worked in a health care or similar setting or who had intimate and prolonged contact with residents of a highly TB-endemic area for ≥6 months. Only perform other screening based on exceptional exposures or knowledge about local outbreaks.

. . . perspectives chapters supplement the clinical guidance in this book with additional content, context, and expert opinion. The views expressed do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC).