Post-Travel Evaluation of the Ill Traveler

Introduction

As many as 43%–79% of travelers to low- and middle-income countries (LMICs) become ill during or after travel. Although most of these illnesses are mild, some travelers become sick enough to seek care from a healthcare professional. Most post-travel infections become apparent soon after returning from abroad, but incubation periods vary, and some syndromes can present months to years after initial infection or after travel. The purpose of this chapter is to guide the healthcare professional's initial approach to the evaluation of the ill returned traveler. Common syndromes observed in returned travelers include acute undifferentiated fevers, respiratory illnesses, acute or chronic gastrointestinal illnesses (including diarrhea and hepatitis), illnesses involving the central nervous system (e.g., meningitis or encephalitis), dermatologic complaints, and eosinophilia (see Post-Travel Respiratory Infections; Post-Travel Diarrhea; Post-Travel Dermatologic Conditions; and Post-Travel Parasitic Disease Includ­ing Evaluation of Eosinophilia chapters). A syndromic approach can help direct the differential diagnosis and diagnostic workup.

Healthcare professionals who manage ill returned travelers are encouraged to stay informed of current outbreaks in the destination countries that their patients visit. A wealth of resources for health care professionals are available on CDC's Travelers' Health website and CDC's Outbreak website; the Program for Monitoring Emerging Diseases International Society for Infectious Diseases; weekly communicable disease threat reports. Several other resources, some free and some by subscription, are also available (see Travel Medicine Resources for Healthcare Professionals chapter).

Triage: ensuring safety and selecting the appropriate level of care

Accurate triage is critical to ensure safety for healthcare professionals, other patients attending the clinic, and the public; to avoid treatment delays; and to select the appropriate level of care for the returned traveler.

Caring for patients with potentially severe, transmissible infections requires enhanced infection control measures (see Post-Travel Evaluation to Rule Out Viral Special Pathogen Infection chapter). These may include personal protective equipment, such as respirators, face masks, eye protection, face shields, gloves, gowns, and head and shoe coverings; contact precautions and barrier nursing (e.g., multidrug-resistant organisms); and care in rooms that are negatively pressured in relation to the anteroom and the corridor (airborne infection isolation) or in facilities with high-level isolation units. To guide infection control precautions needed to safely contain and manage patients with suspected or confirmed high-consequence infectious diseases (HCIDs) including potentially novel pathogens, HCIDs can be divided into contact and airborne groups (Table 10.1.1).

Table 10.1.1: High-consequence infectious diseases (HCIDs)

Most post-travel illnesses can be managed on an outpatient basis. However, some patients might need to be hospitalized (e.g., when clinical presentations with acute respiratory distress, hemodynamic instability, and mental status changes require inpatient care). Management in an inpatient setting is especially vital if reliable follow-up of patients is uncertain or the patient does not have sufficient support at home to assist should the clinical condition rapidly deteriorate. The threshold for admitting patients with undiagnosed undifferentiated systemic febrile illnesses should be low.

Malaria should be ruled out in all patients who develop febrile illness after returning from endemic areas (see Malaria and Yellow Fever Vaccine and Malaria Prevention Information, by Country chapters). Plasmodium falciparum malaria is considered a medical emergency requiring urgent intervention. Failure to promptly diagnose malaria and commence appropriate treatment can lead to rapid deterioration, progression to severe disease, and death.

The post-travel evaluation

After triaging (see above), the initial approach to the ill returned traveler is very similar to other routine clinical evaluations and should include the elements outlined in the sections that follow.

Association of the traveler's illness with (recent) travel

A detailed history focused on the onset and the nature of symptoms can elicit potential diagnostic clues that make etiologic considerations more or less likely. It is important to extend the history beyond a few months before presentation and to include a person's medical condition before travel.

Because of the heterogenous geographic distribution of travel-related infections, details of the itinerary at sub-national level may be important (e.g., malaria is endemic and seasonal in the northeastern KwaZulu-Natal, Mpumalanga, and Limpopo provinces of South Africa, but not in Cape Town). Data from surveillance systems, such as the GeoSentinel network, can assist in identifying the most commonly reported etiologies of illness in travelers returning from specific geographic regions. For additional considerations of major infectious syndromes according to region of travel, see Table 10.1.2.

Table 10.1.2: Common causes of fever by geographic area

In assessing the association of the traveler's illness with the reported itinerary, 3 time intervals must be considered: the time between return and symptom onset; the time between specific exposures and symptom onset; and the time between symptom onset and consultation. Most common travel-associated infections have short incubation periods, and therefore most acutely ill travelers will seek medical attention within 1 month of returning from their destinations. Dengue and other arboviral infections, influenza, and travelers' diarrhea are examples of infections with shorter incubation periods (up to 2 weeks but commonly shorter; see Dengue; Influenza; and Post-Travel Diarrhea chapters). Diseases with incubation periods of 2–6 weeks include viral hepatitis, acute HIV, leishmaniasis, malaria, and typhoid fever, among others (see Hepatitis A; Leishmaniasis; Malaria; and Typhoid and Paratyphoid Fever chapters). Occasionally, infections such as leishmaniasis, malaria, schistosomiasis, strongyloidiasis, filariasis, and tuberculosis might manifest months or even years after a traveler returns (see Schistosomiasis and Tuberculosis chapters). Consider malaria in the differential diagnosis of any patient who traveled to a malaria-endemic area within 1 year of presentation.

Viral hemorrhagic fevers (VHFs), such as infections caused by Arenaviridae (Lassa fever), Bunyaviridae (Crimean-Congo hemorrhagic fever and Rift Valley fever), Filoviridae (Ebola disease and Marburg virus disease), and Flaviviridae (dengue or yellow fever virus), are characterized by fever and bleeding disorders that can progress to shock and death. Incubation periods of VHFs rarely exceed 21 days, and the risk of VHF is therefore negligible if symptoms develop later than that time frame after leaving a VHF-endemic region.

The most common travel-associated infections by incubation period are listed in Table 10.1.3, Table 10.1.4, and Table 10.1.5.

Table 10.1.3: Common travel-associated infections by incubation period, <14 days

Table 10.1.4: Common travel-associated infections by incubation period, 2–6 weeks

Table 10.1.5: Common travel-associated infections by incubation Period, >6 Weeks

History of the present illness

Symptoms

The most common clinical syndromes after travel to LMICs are dermatologic conditions, diarrheal diseases, and systemic febrile illnesses (see Post-Travel Dermatologic Conditions; Travelers' Diarrhea; and Post-Travel Diarrhea chapters). Other common clinical presentations and findings include animal bites and scratches, asymptomatic eosinophilia, and respiratory illnesses (see Zoonotic Exposures: Bites, Scratches, and Other Hazards; Post-Travel Parasitic Disease Including Evaluation of Eosinophilia; and Post-Travel Respiratory Infections chapters). Familiarity with these syndromes, their epidemiology, and their geographic occurrence will help healthcare professionals to develop a differential diagnosis and a management plan (see later in this chapter, Common Clinical Syndromes).

Host susceptibility—immunization and prophylaxis history

When evaluating an ill returned traveler, the susceptibility of the host must be considered. Beyond the obvious characteristics such as age, sex, and prior exposure to travel-associated infectious diseases, the assessment of host susceptibility includes a review of childhood immunizations and the traveler's vaccination history, including COVID-19 vaccination (Table 10.1.6; Table 10.1.7). Migrant populations deserve special consideration because they are frequently under-immunized and vulnerable to vaccine-preventable diseases (VPD; see Post-Arrival Medical Screening for Newly Arrived Refugees, Immigrants, and Migrants chapter). For example, in returning travelers, a history of documented vaccination against hepatitis A and yellow fever would make these diseases highly unlikely causes of hepatitis or jaundice. During 1997–2010, 37,542 returning travelers sought consultation at GeoSentinel clinics; 580 (1.5%) of these travelers were diagnosed with VPDs. The most frequently reported VPDs were hepatitis A, hepatitis B, influenza, and typhoid fever. More than half of the patients with VPD in this study were hospitalized.

Table 10.1.6: Elements of a complete travel history in an ill returned traveler

Table 10.1.7: Vaccinations and precautions

Effective chemoprophylaxis is available to prevent malaria (see Malaria chapter). Travelers with febrile illness returning from malaria-endemic areas should therefore be asked about prescription of and adherence to malaria chemoprophylaxis. Strict adherence substantially reduces the risk of malaria and increases the likelihood of an alternative diagnosis. More than 90% of U.S. residents who acquire travel-associated malaria report not having adhered to a Centers for Disease Control and Prevention (CDC)-recommended chemoprophylaxis regimen. Regardless of chemoprophylaxis history, in travelers with febrile illness returning from malaria-endemic areas, the diagnosis should always be ruled out by appropriate diagnostic testing.

Host susceptibility—comorbidities

Underlying illnesses can affect a traveler's susceptibility to infection as well as the clinical manifestations and disease severity (see Travelers with Chronic Illnesses chapter). Traveling can exacerbate underlying conditions, such as diabetes, chronic lung disease, inflammatory bowel disease, and ischemic heart disease, through change of diet, change of time zones, or physical and environmental factors. In addition, an increasing number of international travelers are immunosuppressed, whether due to HIV infection, treatment with immune-modulating medications, organ transplant, or other primary or acquired immunodeficiencies (see Travelers with HIV and Immunocompromised Travelers chapters).

Evaluation of risk factors related to travel

Travel destination(s), itinerary, and travel duration

Travel destinations and itineraries are the main determinants of the infectious hazards that travelers are exposed to. Travel duration is also a factor because the risk for a travel-associated illness increases with the duration of the journey.

Knowledge of the prevalence of common etiologies of travel-associated infections in specific areas (e.g., rural vs. urban, highlands vs. lowlands) in the region of travel is essential to estimate pre-test probabilities of differential diagnostic considerations and should be used to guide the diagnostic workup of the ill returning traveler.

Surveillance data (e.g., from the GeoSentinel network) show that the frequency of etiologic diagnoses varies depending on the region of the world visited. Among returning travelers with fevers, for example, dengue was diagnosed most frequently among travelers returning from Asia, while malaria was diagnosed most frequently among travelers returning from Africa. Online resources may be helpful, or a travel medicine specialist can assist with formulating a differential diagnosis and might be aware of outbreaks or the current prevalence of an infectious disease in an area (see Travel Medicine Resources for Healthcare Professionals chapter).

Infections with typical seasonal transmission in the United States might occur at different times of the year, or throughout the year, in other regions. For example, influenza transmission can occur throughout the year in tropical areas, and the peak season in the Southern Hemisphere is during the Northern Hemisphere late spring or early summer and into the fall (see Influenza chapter); healthcare professionals in the Northern Hemisphere should therefore be alert to the possibility of influenza outside the usual wintertime influenza season among returning travelers. Malaria and arboviral infections may be seasonal in many regions, related to variations in temperature and rainfall.

Travel type

Common reasons for travel are tourism, visiting friends and relatives, business, humanitarian aid, study or volunteering abroad, expatriate work, medical care, and migration (see Visiting Friends and Relatives: VFR Travel; The International Business Traveler; Humanitarian Aid Workers; Study Abroad and Other International Student Travel; Pre-Arrival Medical Screening and Interventions for Newly Arrived Refugees, Immigrants, and Migrants; Medical Tourism; and Post-Arrival Medical Screening for Newly Arrived Refugees, Immigrants, and Migrants chapters). The type of travel is relevant for risk assessment because it is closely related to other determinants of infectious disease hazards, such as access to pre-travel consultations, adherence to vaccination recommendations and preventive measures (including malaria chemoprophylaxis), and exposures (e.g., staying with local populations or family, food preparation practices, attending mass gatherings or funerals), or lack thereof (e.g., short business meetings at luxury hotels in the major cities of LMICs). VFR travelers are at greater risk for malaria, typhoid fever, parasitic infections, and tuberculosis, often because VFR travelers stay longer, travel to more remote destinations, have more contact with potentially contaminated food and water sources, and may not receive pre-travel advice (see Visiting Friends and Relatives: VFR Travel and The Pre-Travel Consultation chapters). Travelers backpacking and camping in rural areas have a wider range of exposures than those staying in luxury, air-conditioned hotels (see Adventure Travel chapter).

Exposures

A key component of a travel history is an assessment of potential exposures to sources of infection and whether fellow travelers are also ill. Screening for exposures requires a detailed inquiry about bites, environmental hazards, ingestions, and sexual risk behaviors. Examples of these exposures are animal bites (insects, arachnids, mammals), engagement in activities (e.g., fresh or saltwater swimming, hiking, visiting caves, mass gatherings), details of the traveler's diet (e.g., eating street food, bushmeat, unpasteurized dairy products, bottled or tap water), and sexual behaviors (see Zoonotic Exposures: Bites, Scratches, and Other Hazards; Mass Gatherings; and Sex and Travel chapters). Of note, 20%–34% of male international travelers engage in casual sex abroad, and 43%–49% of all travelers participating in casual sex abroad have condomless sex.

Leptospirosis and schistosomiasis are examples of infections that can be acquired through freshwater bathing, swimming, or wading (see Leptospirosis and Schistosomiasis chapters). Travelers may not always recall arthropod bites, but a history of a tick bite could suggest a diagnosis of tick-borne encephalitis or African tick bite fever (or other rickettsial infections; see Tick-Borne Encephalitis and Rickettsial Diseases chapters). Tsetse flies (genus Glossina, family Glossinidae) are the insect vector for transmission of Trypanosoma brucei, protozoans that cause African sleeping sickness. Tsetse flies are large, and their bites are painful; thus, patients often recall being bitten (Table 10.1.8).

Table 10.1.8: Causes of fever associated with specific exposures

A class of exposures that should not be overlooked is encounters with health care abroad (see Medical Tourism, and What to Do When Sick Abroad chapters). These may result from acute travel-related illness, from exacerbations of preexisting conditions, or from plans made in advance to obtain care at the destination. Details of any illness episodes and healthcare encounters while traveling, as well as use of antimicrobials or other medications, are essential to follow-up diagnosis and management of the ill returning traveler. International travel plays a key role in the spread of highly resistant microorganisms. Travelers can become colonized or infected by bacteria resistant to commonly used antibiotics. Bacteria that produce extended-spectrum beta-lactamases and carbapenemases, including bacteria expressing the metalloprotease NDM-1, have caused infections acquired during travel, sometimes related to elective or emergency medical care. Travelers to South and Southeast Asia are at particularly high risk of acquiring multidrug-resistant Enterobacterales. Enteric fever (typhoid or paratyphoid fever) has become increasingly resistant to fluoroquinolones, third-generation cephalosporins, and azithromycin, especially in Asia (see Typhoid and Paratyphoid Fever chapter).

Physical examination

A complete physical examination, including vital signs (e.g., blood pressure, heart rate, body temperature) and assessment of mental status, should be performed on any ill returned traveler.

Presence of fever plus certain associated signs, symptoms, or laboratory findings can suggest specific infections (Table 10.1.9). Findings that should prompt urgent attention include hemorrhage, low blood pressure, altered consciousness, and high respiratory rate. Even if an initial physical examination is unremarkable, repeat the exam at least daily if the diagnosis is not clear because new findings might appear that will help in the diagnostic process (e.g., skin lesions, a tender liver). Although most febrile illnesses in returned travelers are secondary to infections, other conditions, including pulmonary emboli and drug hypersensitivity reactions, also can be associated with fever.

Table 10.1.9: Clinical findings in febrile infectious diseases after travel

Fever as part of a clinical syndrome deserves further scrutiny because it could indicate a disease of public health concern for which infection containment and control measures are indicated (Table 10.1.10). On the other hand, it is not uncommon to have no focal findings in infections such as malaria, typhoid fever, or dengue, so-called undifferentiated (or systemic) febrile illnesses. Nevertheless, this distinction provides only a rough guide. For example, malaria may sometimes be accompanied by a variety of focal symptoms. Misdiagnosing a patient with gastroenteritis who actually has malaria with gastrointestinal symptoms could negatively impact the patient's outcome.

Table 10.1.10: Febrile syndromes in travelers: Potential diseases of public health concern requiring immediate infection-control measures

Dermatologic presentations are among the most frequent conditions in returned travelers (see Post-Travel Dermatologic Conditions chapter). Skin rashes may evolve rapidly, and the localizations and types of skin lesions (e.g., macules, nodules, papules, plaques, ulcers) can contribute to the diagnosis of systemic infections, such as arboviral infections, measles, spotted fever group rickettsioses, typhoid fever, acute schistosomiasis (Katayama fever), or acute HIV infection. Petechial or purpuric lesions may indicate meningococcal disease, rickettsiosis, or viral hemorrhagic fever. The presence of a single or multiple eschars, mildly painful black necrotic lesions with a red rim that are frequently associated with localized lymphadenopathy, in a traveler returning from southern Africa, is highly suggestive of African tick bite fever, a rickettsiosis transmitted by the bite of hard ticks (Hyalomma spp.). Other rickettsioses predominate in other regions. The physical exam should include a thorough inspection of the skin, including skin folds and genital areas that are frequently overlooked.

Establishing a differential diagnosis

Most illnesses in returned travelers (e.g., diarrhea, pneumonia, or pyelonephritis) are caused by common and cosmopolitan infections that must be considered along with the more unusual ones. The differential diagnoses of these common conditions should be expanded in accordance with the travel-related risk factors outlined above. These include pre-travel preparation and adherence to preventive measures, the geographic area of travel, activities and exposures during travel, and type of travel (Table 10.1.2; Table 10.1.8).

Exploring the time relationship between return and symptom onset, between specific exposures and symptom onset, and between symptom onset and consultation can help narrow the differential diagnosis by evaluating these against the characteristic incubation periods of potential causative pathogens (Table 10.1.3; Table 10.1.4; Table 10.1.5).

Common clinical syndromes

Salient points and descriptions of febrile illnesses and common clinical syndromes are outlined below. Always keep infection control, public health implications, and requirements for reportable diseases in mind.

Fever in returning travelers

Fever often accompanies serious illness in returned travelers. Because an elevated temperature can signal a rapidly progressive infection, early and immediate evaluation should be initiated (Box 10.1.1). Additionally, an increasing number of travelers are older or have significant comorbidities, and the risk of serious morbidity is augmented in these groups.

Given the potential for rapid deterioration, a differentiation between malarial and non-malarial illness is helpful in the initial approach of febrile returned travelers, especially when they have visited areas with malaria in the months preceding the consultation. Another important decision point is whether the infection is treatable. Rapid diagnosis and treatment of malaria, as well as enteric fever and rickettsial infections, can reduce morbidity and adverse clinical outcomes (see Malaria; Typhoid and Paratyphoid Fever; and Rickettsial Diseases chapters). Targeted antiviral treatments for arboviral infections are not available, but diagnosis can inform prognosis and guide management as well as presumptively exclude other etiologies of acute fever. Most illnesses which are of immediate public health concern (e.g., Middle East respiratory syndrome, COVID-19, tuberculosis, hemorrhagic fevers) generally present with suggestive signs, symptoms, or exposure histories. Another important example is acute HIV infection, which is highly transmissible in the early symptomatic phase.

A specific cause for fever is not identified in ≥25% of returned travelers. It is often reasonable to suspend further diagnostic testing when symptoms resolve spontaneously.

Box 10.1.1

Malaria

Malaria is the most common life-threatening tropical disease associated with fever in returned travelers (see Malaria chapter). In the United States, approximately 2,000 cases of malaria are diagnosed each year. More than 90% of reported cases of P. falciparum malaria manifest ≤30 days of return, whereas almost half of cases of Plasmodium vivax malaria manifest >30 days after return. Malaria (especially P. falciparum) can progress rapidly and therefore requires prompt evaluation and initiation of treatment. A history of taking malaria chemoprophylaxis does not exclude the possibility of malaria. Patients with malaria can be afebrile at the time of evaluation but typically give a history of fever or chills. Occasionally, malaria presents with prominent respiratory (including acute respiratory distress syndrome), gastrointestinal, or central nervous system symptoms.

In the United States, severe malaria, defined as vital organ involvement including shock, pulmonary edema, significant bleeding, seizures, impaired consciousness, or laboratory abnormalities, such as kidney impairment, acidosis, anemia, and high parasitemia, occurs in approximately 10% of patients with malaria, and around 0.3% of those receiving a diagnosis of malaria die.

Non-malarial febrile illness

Arboviral infections

Dengue is the most common cause of febrile illness among people who seek medical care after travel to Latin America or Asia (see Dengue chapter). Other arboviral infections have emerged as causes of fever in travelers, including chikungunya and Zika (see Chikungunya and Zika chapters).

Common infections

Do not overlook common infections (e.g., diarrheal illnesses, pneumonia, pyelonephritis) in the search for exotic diagnoses.

Fever and bleeding

Viral hemorrhagic fevers other than dengue (e.g., Ebola disease, Lassa fever, Marburg virus disease) are important to identify but are rare in travelers. Because of the need to institute prompt, specific treatment, always consider the possibility of bacterial infections (e.g., leptospirosis, meningococcemia, rickettsial infections) that can also cause fever and hemorrhage (see Leptospirosis; Meningococcal Disease; and Rickettsial Diseases chapters).

Undifferentiated fever

Undifferentiated fever is a term usually referring to fever without localizing symptoms or signs, or with symptoms and signs which are non-specific or relatively mild. These may include headache, malaise, non-specific rash, or relatively mild cough and gastrointestinal symptoms. The term is meant to exclude common causes of fever, such as meningitis, pneumonia, viral respiratory infections, urinary tract infections, acute gastroenteritis, soft tissue infections, and so on. The "classic" fever patterns associated with specific infections often do not present until later in the illness and therefore cannot be used to guide management of the acutely febrile patient. For example, the alternate-day fevers seen in vivax or ovale malaria typically do not occur before the second week. Similarly, "relative bradycardia" (relatively low pulse rate in the face of high fever) is often not seen in the acute phase of enteric fever.

The differential diagnosis of travel-associated undifferentiated febrile syndromes includes common "cosmopolitan" etiologies such as Epstein-Barr virus, cytomegalovirus, and toxoplasmosis. Malaria, dengue, and enteric fever comprise nearly three-quarters of identified etiologies in several case series. The prevalence of the most common causes of fever in returning travelers varies with the regions of exposure (Table 10.1.2). When diagnosing febrile illness in travelers, current knowledge of ongoing outbreaks in destination countries is essential (see Introduction).

Antimicrobial-resistant organisms

Travelers could be infected or colonized with drug-resistant pathogens, especially travelers who were hospitalized abroad or who took antimicrobial agents to treat travelers' diarrhea.

Animal bites and scratches

Promptly evaluate any traveler who reports animal bites or scratches for risks of infection or envenomation (see Zoonotic Exposures: Bites, Scratches, and Other Hazards and Poisonings, Envenomations, and Toxic Exposures During Travel chapters, for recommendations on wound care and case management). Consider travelers with mammal bites or scratches in an endemic country as being at high risk for rabies exposure and provide rabies post-exposure prophylaxis, as indicated (see Rabies chapter). If the traveler was exposed to a macaque, B virus post-exposure prophylaxis with valacyclovir might be indicated.

Asymptomatic eosinophilia

Parasitic infections are rare in most travelers, so other etiologies for eosinophilia must be considered (see Post-Travel Parasitic Disease Including Evaluation of Eosinophilia chapter). A common cause is drug-induced eosinophilia (including antimicrobials, anticonvulsants, anti-inflammatories, immunomodulators, and antimalarial prophylaxis [chloroquine, mefloquine, and proguanil]). Allergic conditions, hematologic disorders, and some viral, fungal, and protozoan infections also can cause eosinophilia. Eosinophilia can be pronounced early in helminthic infections, and usually coincides with larval migration through tissues (e.g., pulmonary transit of Ascaris, hookworm, Strongyloides [Löffler syndrome], schistosomiasis), which then slowly decreases over time.

Other nematode infections associated with eosinophilia include lymphatic filariasis, chronic strongyloidiasis, acute trichinellosis, and visceral larva migrans. These infections might be asymptomatic but also could have associated symptoms (e.g., rash, swelling). See Section 4 for more information on specific diseases. Protozoa, in general, do not cause eosinophilia, with the exception of Cystisospora belli and Sarcocystis spp.

Respiratory illnesses

Respiratory illnesses are frequent among returned travelers and are typically associated with common respiratory viruses that spread from person to person, primarily through respiratory transmission but also through fomites (see Post-Travel Respiratory Infections chapter). Among the most common VPDs associated with international travel are influenza and COVID-19 (see Influenza and COVID-19 chapters). Depending on geography and seasonality, influenza illnesses can occur throughout the year and may be diagnosed in returning travelers outside the usual time frame expected in their home country.

A special caveat is reserved for other emerging respiratory diseases (e.g., avian influenza, Middle East respiratory syndrome) in the differential diagnosis. These are potentially severe, transmissible infections, and management of infected patients may require enhanced infection-control measures and specialized diagnostics. In suspected cases, alert local public health authorities and the CDC immediately. See relevant chapters in Section 4 for more information on these emerging infections (Table 10.1.9).

Delayed illness onset or chronic cough after travel could indicate tuberculosis, especially in a long-term traveler or healthcare worker. Helminth infections associated with pulmonary symptoms include Ascaris, hookworms (Ancylostoma or Necator), paragonimiasis, schistosomiasis, and strongyloidiasis (see Schistosomiasis chapter).

Sexually transmitted infections

Sexually transmitted infections, including acute HIV, can cause acute febrile infections (see Sex and Travel chapter). While antibody-based tests are useful for HIV screening in most non-travel scenarios, such tests may be negative during the first weeks of infection in a traveler. Diagnostic testing should include antigen detection (commonly integrated into many screening tests) or, very early in infection, could be done with a nucleic acid-based test, such as an HIV viral load assay.

Further laboratory testing

Diagnostic testing in returning travelers should be based on the differential diagnosis and a sound knowledge of common clinical syndromes in post-travel medicine in order to confirm or exclude diagnoses that have direct consequences for individual case management or an immediate impact on public health.

Returning travelers who present with undifferentiated fever after visiting a malaria-endemic country within the prior year should have malaria testing results available urgently, ideally within a few hours (see Malaria chapter). Conventional testing for malaria should be repeated 2 or 3 times over the first 24–48 hours in the absence of an alternate diagnosis, as low parasitemia in the early stages may be missed. Nucleic acid amplification tests are more sensitive and do not need to be repeated but are not commonly available in the United States. Blood cultures should be taken, especially in patients with undifferentiated fever. Enteric fever is an important travel-associated illness that is almost always diagnosed by appropriate blood culture. Isolation of the causative Salmonella enterica serovars Typhi or Paratyphi is essential to evaluate the antimicrobial susceptibility of these strains because antimicrobial resistance is increasingly common in many regions (see Typhoid and Paratyphoid Fever chapter). Arbovirus infections are best diagnosed by RT-PCR in the acute febrile phase, although a dengue rapid antigen test is also reliable. Rickettsioses and leptospirosis are typically diagnosed by serology, but acute serology is not highly sensitive or specific (see Rickettsial Diseases and Leptospirosis chapter). HIV testing should be offered to all febrile patients.

When routine testing fails to yield a diagnosis, storing extra tubes of serum or whole blood for further testing (paired antibody detection in acute and convalescent sera or nucleic acid testing in acute sera) is often helpful. Respiratory specimens for a multiplex PCR respiratory virus panel should be considered in all patients with fever, coryza, and myalgia.

A complete blood count with differential can detect anemia, eosinophilia, leukocytosis, leukopenia, or thrombocytopenia. Thrombocytopenia is often present in dengue, malaria, and acute HIV but is also seen in severe sepsis. The total white cell count is often low or normal in malaria, dengue, and enteric fever. A complete metabolic profile, including creatinine, urea, liver enzymes, blood glucose, and coagulation screen, is frequently useful to identify electrolyte disturbances or renal, liver, or systemic involvement. The risk to laboratory workers from processing samples in routine equipment is very low, and delaying these tests is rarely indicated. These tests often can help narrow the differential diagnosis and determine disease severity.

Specialty consultation

Consult an infectious disease specialist when managing complicated or severe travel-associated infections or when the diagnosis remains unclear. A tropical medicine or infectious disease specialist should be involved in cases that require specialized diagnostics or treatment (e.g., leishmaniasis, severe malaria, neurocysticercosis).

Involve local, state, and federal public health authorities whenever managing transmissible, high-consequence infections. CDC provides on-call assistance with the diagnosis and management of many diseases (see CDC Contact Information for Healthcare Professionals, inner flap). During non-business hours or for other conditions, call the CDC Emergency Operations Center at 770-488-7100.