Screening Asymptomatic Returned Travelers
CDC has no official guidelines or recommendations for screening asymptomatic international travelers. (For recommendations regarding the screening of newly arrived immigrants and refugees, see Chapter 8, Newly Arrived Immigrants & Refugees.) Nevertheless, the screening of travelers returning from developing countries represents a substantial portion of the activity of many travel and tropical medicine clinics. The scientific literature on the cost-effectiveness of screening asymptomatic travelers is sparse. It is clear that 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. Local medical practitioners will have little familiarity with the associated diseases, and specific diagnostic tests may not be readily available or may have poorly defined operating characteristics. The decision to screen for particular pathogens will depend on the type of travel, itinerary, and exposure history. However, exposure history is often unreliable and poorly predictive of infection, the value of a detailed itinerary is limited by incomplete information on where pathogens are endemic, and the type of travel often does not provide a practical assessment of risk.
Screening traditionally has been viewed as a secondary prevention intervention, that is, an attempt to identify existing occult illnesses or health risks. The cost effectiveness of screening involves a consideration of the natural history of the problem, the predictive value of the test, the direct and indirect costs of the test, and the effectiveness of prevention or therapy. Because of convenience and the susceptibility to suggestion at the time of screening, the screening visit may also offer an opportunity to promote primary prevention by discussing behavioral or other risk factors predisposing to ill health. These may include, for example, counseling on sexual health or the avoidance of schistosomiasis or malaria.
Travelers are often most concerned with the possibility of occult parasitic infection. Unfortunately, when screening for parasitic disease, the literature shows that patient questionnaires and common laboratory testing 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 unrewarding.
Most commonly, a stool examination is performed, typically microscopy. Several molecular assays are commercially available; these detect a panel of viral, bacterial, and parasitic (protozoal) pathogens. In some cases these panels are more sensitive than traditional testing methods, and even asymptomatic people are often 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. Travelers are often concerned about “worms,” by which they mean intestinal nematodes. However, probably because of hygiene and short duration of exposure for most travelers, infections with large numbers of the common nematodes, such as Ascaris, Trichuris , or hookworm, are rare. Questioning returning expatriates infected with intestinal helminths has disclosed no attributable symptoms compared with uninfected controls, although there have been case reports of complications, such as migration of Ascaris into the biliary system. The life cycles of almost all helminths preclude any real risk of ongoing transmission from asymptomatic hosts in developed countries. Helminths generally have a natural lifespan of months to a few years, which ensures eventual spontaneous clearance and are of limited clinical importance when present in low intensity infection, though in rare cases aberrant migration of Ascaris might result in clinical disease. The exception to this rule is Strongyloides . For this helminth, serious complications are well known, nonspecific symptoms may easily be overlooked, duration of carriage after infection is unlimited, and the original burden of infection is irrelevant. Unfortunately, diagnosis by stool examination is notoriously insensitive, and serologic methods are often required, as discussed below. Molecular panels for helminths are at the research stage of development.
The finding of pathogenic protozoa in asymptomatic patients is of questionable significance (with the possible exception of Entamoeba histolytica , a rare finding in these travelers). History of exposure to contaminated food or water has poor predictive value. There is no evidence to suggest that these asymptomatic carriers are likely to develop symptoms at a later time. Certainly, the medications used to treat pathogens have their own adverse effects. In theory, these carriers pose a public health risk, although transmission by asymptomatic travelers appears to be rare. This is further complicated by the fact that stool microscopy for protozoa is expensive, not very sensitive, and not highly reproducible, and many laboratories have limited expertise. Entamoeba histolytica cannot be distinguished from E. dispar by microscopy, requiring 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. Commercial molecular methods to screen stool specimens for multiple pathogens simultaneously typically include several protozoa, generally with sensitivity at least as good as microscopy, and offer rapid turnaround times of several hours, although costs remain high. Some of these panels are sensitive for questionably pathogenic organisms, such as Blastocystis and Dientamoeba . Identifying these may lead to patient anxiety and unnecessary treatment.
Among the helminths capable of causing eventual illness in asymptomatic travelers, most emphasis has been given to Strongyloides and the parasites that cause schistosomiasis and filariasis. There is no evidence that the low-burden schistosomal infections typically found in travelers are likely to lead to the types of complications commonly found in endemic areas, such as liver fibrosis or malignancy. Nevertheless, this possibility cannot be entirely ruled out, particularly in those who may have more intense exposures. Even brief exposures to freshwater lakes and rivers in known endemic foci in Africa are associated with substantial seroconversion rates. In addition, complications due to ectopic egg migration can occur in light infections and without warning. On the other hand, reports of travelers with late complications from asymptomatic filarial infections are virtually nonexistent. Traditional tests for the parasites that cause these infections, including stool examination for Strongyloides and Schistosoma spp., urine for S. haematobium , and blood or skin snips for microfilaria, all lack sensitivity, particularly in low-burden infection. For this reason, serologic testing has been advocated as the best screening tool. The problems with serologic screening include expense, lack of easy availability, and lack of standardization. Serologic tests are often 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 strongyloidiasis and schistosomiasis, treatment is cheap, easy, and effective. The common antihelminthic agents, such as ivermectin, albendazole, and praziquantel, have excellent safety profiles. Nevertheless, rare but severe adverse events can occur when certain occult, unsuspected parasitoses are present, such as ivermectin and loiasis or albendazole and neurocysticercosis. While it is not clear who should be screened, it is logical to at least perform serologic tests on travelers with a high duration and risk of exposure and to treat all those found to be positive. Since asymptomatic filarial infections appear least likely to have sequelae, and treatment is often neither very effective nor easy, the threshold for filarial serology (or antigen testing in the case of Wuchereria bancrofti ) should be higher. Serology usually only becomes positive after adult forms have matured, which means waiting for 3 months or so after exposure. Serology for these pathogens are available at the parasitic diseases laboratory at CDC (www.dpd.cdc.gov/dpdx; 404-718-4745; email@example.com). Serology for filarial infection is available as well through the NIH laboratory (301-496-5398).
Screening for eosinophilia is a common test, since it is quick, universally available, and theoretically of value in detecting invasive helminths, if not protozoa. However, multiple studies have shown eosinophilia to have poor sensitivity. Specificity can be high; however, the low prevalence of infection in asymptomatic travelers means positive predictive value is low. In addition, the finding of eosinophilia may lead to an extensive and often fruitless search for a cause, generating high costs. Many cases of eosinophilia resolve spontaneously, possibly because of infection with nonpathogenic organisms or a noninfectious cause, such as allergy or drug reaction. Eosinophil counts may be repeated after several weeks or months before embarking on an extensive investigation. Counts may be highly variable, even within a single day, and are suppressed by endogenous or exogenous steroids. Evaluation of absolute counts, rather than by percentage of leukocytes, is more reproducible and predictive.
Immigrants with frequent and regular exposure to malaria may gradually develop partial immunity. This may result in low-level parasitemia with few or no symptoms. They may later recrudesce with more severe illness. This phenomenon is rare in other travelers. There is no justification for screening most asymptomatic travelers, whether by blood film, serologic tests, or molecular methods. No available tests can detect latent infections with Plasmodium vivax or P. ovale . Travelers should be reminded to seek evaluation for unexplained fever and notify practitioners of any recent travel.
Occult trypanosomiasis in asymptomatic travelers (as opposed to immigrants) appears to be extremely rare. Screening tests, such as serology and molecular diagnostics, are of unknown value. For travelers to endemic areas of Latin America, testing might be considered in cases of prolonged residence in primitive housing, such as mud walls and thatched roofs, especially if reduviid bugs have been seen. East African trypanosomiasis has affected travelers but typically causes symptoms. West African disease is generally not reported in travelers. Other parasitic infections rarely seen in returning travelers include neurocysticercosis, fascioliasis, paragonimiasis, and others. Primary care providers should refer patients suspected of having these infections to an infectious diseases specialist.
Sexual activity and travel seem to be linked. High rates of contact with new partners, including sex workers, have been documented in volunteers, expatriate workers, backpackers, and military personnel. Of concern are the low rates of reported condom use. Returning travelers with acute HIV or hepatitis B infection pose public health risks. Travelers may be hesitant to volunteer a relevant history. Screening for sexually transmitted infections should always be considered.
The incidence of tuberculosis related to travel is difficult to estimate. Estimates of exposure based on skin test (Mantoux) conversions suggest rates of exposure of the same general magnitude as the local population. Work in high-prevalence settings such as health care institutions or refugee camps merits screening. Traditionally, this has been done using pre- and post-travel skin tests. This is cumbersome, requiring as many as 4 pretravel visits for a 2-step test and 2 visits after potential exposure. This number can be reduced by using the more expensive interferon-γ release assay (IGRA), which also is less subject to false-positive results related to BCG vaccination. Unfortunately, recent data suggest that IGRA results show inadequate reproducibility, leading to false “conversions” on follow-up testing. In most patients born and raised in low-prevalence countries, a case can be made for omitting the pretravel test, because results are rarely positive.
For many long-term travelers, such as expatriate workers and some missionary and aid workers, the visits for asymptomatic screening may also be their only interludes from a continuing assignment abroad allowing for a general health evaluation. The usual recommendations for the periodic health exam, which may include screening for hypertension, diabetes, and malignancy, would apply. These visits also provide an opportune time to review vaccination status, malaria prophylaxis, and health behaviors.
Recommendations for screening the asymptomatic traveler are necessarily based on opinion and common sense, rather than convincing evidence. The following may serve as a general guideline.
For the asymptomatic short stay (<3–6 months) traveler, the yield of screening is low 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. Exposure to fresh water in a region endemic for schistosomiasis, especially in Africa, merits serologic screening, with the addition of stool and urine examination in the case of high-intensity exposure. Serology for Strongyloides should be considered in those who have a high risk of skin exposure to soil likely to be contaminated with human feces, usually those with a history of frequently walking barefoot outdoors. A sexual history should be obtained, and screening for sexually transmitted and bloodborne infections is often warranted. Work in a health care setting or other area at high risk for TB may merit screening.
For longer-stay travelers, as the overall yield of screening increases it becomes less useful to rely on history for selective testing. The emphasis should be on those with the longest stays and the most problematic sanitary conditions. In some cases, employers may require certain tests, partly for reasons of liability. Stool examinations are usually done, although they serve mostly to provide a psychological reassurance. Serologic testing for schistosomiasis and strongyloidiasis should be done in those with recent or remote travel histories to endemic areas and reporting some level of risk. Eosinophil counts are usually done, although results should be interpreted cautiously. Screening for sexually transmitted and bloodborne infections including HIV, hepatitis B and C, gonorrhea, chlamydia, and syphilis should be offered to all except those with the most convincing absence of risk. Mantoux or IGRA tests should be limited to those who have worked in a health care or similar setting, or who have had intimate and prolonged contact with residents of an endemic area for ≥6 months. Any other screening should be guided by exceptional exposures or knowledge about local outbreaks.
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