The Immunocompromised Traveler

Enteric Infections

Pathogens that enter via the gastrointestinal tract pose considerable threat to the immunocompromised traveler, as both intestinal mucosal and systemic defenses against gut pathogens are diminished. Decreased gastric acid and diminished local immune response mean that a smaller inoculum may be needed to establish infection. Once established, infection may be more severe and difficult to cure. The consequences of even typical traveler's diarrhea may be more profound for the immunocompromised patient. For PHAs taking antiretroviral therapy, nausea may be significant and interfere with the tolerability of their usual drug regimen. Infections with Salmonella , Shigella , and Campylobacter species tend to be chronic and relapsing and can lead to bacteremia. Salmonellosis in particular may be characterized by recurrent bacteremias. Campylobacteriosis, cryptosporidiosis, and microsporidiosis may extend into the biliary tree, making clearance more challenging. An important opportunistic pathogen to be aware of is Strongyloides (see Chapter 45 ). This infection is commonly found in tropical climates including the southeastern United States, acquired through the skin when travelers come into direct contact with fecally contaminated soil. Strongyloides is usually asymptomatic or causes mild diarrhea symptoms and a transient recurrent rash called larva currens. In immunosuppressed individuals, however, it can more readily cause acute hyperinfection syndrome. Strongyloides can also lie dormant for years to decades after initial infection. Cases of reactivated strongyloidiasis hyperinfection may happen after patients receive immunosuppression with even short courses of corticosteroids; most of these cases have been fatal. Table 15.2 summarizes some of the enteric infections frequently encountered by travelers and indicates increased morbidity in immunocompromised persons, relative to the general population. Of note, increased risk was most notable in the pre-HAART era and likely reflects risk in patients with advanced HIV. Risk in relatively immunocompetent patients on effective ART may be similar to that of the general population.

Respiratory Infections

Respiratory tract infections are common during travel, although the etiology is usually undefined. Several outbreaks of influenza in travelers have been documented, necessitating vaccination and early treatment (both will be discussed later in this chapter). Legionnaires' disease is acquired from stagnant or poorly cleaned water sources and has infected travelers staying at resort hotels and using spa facilities in several locations, including Europe and the Caribbean. Outbreaks of influenza and legionellosis on cruise ships document another possible place of transmission.

Two geographically focal fungal infections, histoplasmosis and coccidioidomycosis, can be progressive and disseminate in immunocompromised persons. Infection occurs via inhalation of air-borne organisms. The endemic area for coccidioidomycosis includes the southwestern United States, Mexico, and Central and South America. Although the largest number of reported cases of histoplasmosis has been in the United States, the disease has been reported in all continents, and the organism is an important cause of disseminated disease in PHAs in the Caribbean and parts of Central and South America. Another soil-associated fungal pathogen, Penicillium marneffei , found in Southeast Asia and China, is one of the most common opportunistic infections in northern Thailand. Travelers to this region who become infected may manifest symptoms as early as 4-5 weeks and as late as 10 years or more after exposure. Immunocompromised travelers to areas where these fungi are endemic should take precautions to avoid inhaling dust or entering caves; if heavy or long-term exposure is unavoidable, prophylaxis with fluconazole (100 mg/day) for coccidiomycosis or itraconazole (200 mg/day) for histoplasmosis and penicilliosis may be used.

Immunodeficient persons are exquisitely susceptible to tuberculosis. Patients receiving anti-tumor necrosis factor (TNF) therapy are at particularly higher risk of tuberculosis reactivation. Up to 10% of HIV-infected persons with latent tuberculosis will develop active infection. The likelihood of exposure to tuberculosis in many developing countries (where annual incidence rates may exceed 100/100,000 population) is substantially higher than in the United States (with annual incidence rates <10/100,000 population). Rarely, transmission has also been documented during travel (e.g., airplane, bus, train, boat). Vaccination with attenuated bacillus Calmette-Guérin (BCG) is neither routine nor recommended in the United States, so avoidance of infection and early identification of latent tuberculosis infection are paramount. Tuberculin skin testing (TST) should be done routinely in all immunosuppressed persons, regardless of travel plans (see Chapter 25 ). An induration of 5 mm is considered positive in HIV-infected persons, organ transplant recipients, and those on immunosuppressive medications (equivalent of 15 mg prednisone). The TST should be repeated 2-3 months after prolonged stays in high-incidence areas, which include many parts of Africa and Asia. A period of 4-12 weeks after exposure is generally required for development of delayed-type reactivity to the TST; however, some patients may develop primary clinical disease prior to skin test conversion. Immunocompromised persons should avoid prolonged stays in areas where ventilation is poor, tuberculosis rates are high, and multidrug resistance is common. Newer interferon gamma release assays (IGRA) to detect latent tuberculosis infection are being used with increasing frequency. Neither the TST nor the IGRA is entirely reliable in any population, but they are of particularly limited utility in those with severe immune deficiencies, because of the increased possibility of anergic responses.