Hantaviruses have a global distribution and patients typically present with hemorrhagic
(petechiae, mucosal bleeding diathesis, capillary leak) and/or renal disease. Other variably
present clinical features that may help to distinguish HPS from more common causes of severe
respiratory infections include the absence of sore throat and cough (as seen with influenza)
and radiographic evidence of lobar infiltrates (as seen with bacterial pneumonia) (61).
Dizziness, nausea or vomiting, absence of cough, thrombocytopenia, decreased serum
bicarbonate, and hemoconcentration were present among all HPS patients described in one
case series (61). Several recent studies have confirmed these findings as clinical predictors of
HPS (62). In one study, ribavirin given at a loading dose of 33 mg/kg (maximum 2 g), followed
by either 16 mg/kg (maximum 1 g) every six hours for four days or 8 mg/kg (maximum 0.5 g)
every eight hours for three days reduced mortality sevenfold in patients with hantaviral
hemorrhagic fever with renal syndrome (HFRS). However, efficacy was not demonstrated in a
randomized controlled trial for HPS (63,64).Burkholderia pseudomallei(melioidosis) has rarely
been reported as a cause of fulminant disease in travelers from Southeast Asia and Australia
and more commonly presents as a chronic granulomatous illness resembling tuberculosis (65).
The spectrum of disease in melioidosis ranges from asymptomatic infection to chronic
debilitating illness to fulminant septicemia. The recommended treatment for melioidosis is
intravenous ceftazidime (or imipenem) followed by a prolonged course of oral cotrimoxazole
plus doxycycline to prevent relapse (66,67). Plague may present in either a bubonic (i.e., tender,
fluctuant adenopathy with systemic illness), septicemic, or pneumonic form. Although there
are no recently documented reports of plague in international travelers, one needs to consider
this diagnosis among travelers with a compatible clinical syndrome returning from endemic
areas (e.g., India, Vietnam, Myanmar, Zaire, and Madagascar) (68,69). Patients with plague can
present with symptoms ranging from a mild febrile illness with a bubo to fulminant sepsis.
Given the potential for rapid deterioration as well as contagious spread by respiratory
droplets, prompt institution of appropriate therapy (e.g., gentamicin 2 mg/kg loading dose
then 1.7 mg/kg every eight hours) is critical. A large outbreak of acute pulmonary
histoplasmosis recently occurred among students returning from Mexico (70). Their exposure
toHistoplasma capsulatumapparently occurred at a hotel where maintenance projects were
underway. Other endemic mycoses, such as coccidioidomycosis and penicilliosis (especially
within HIV patients), are also considerations in the differential diagnosis of a febrile
respiratory illness in a returning traveler (71).
Severe acute respiratory syndrome (SARS), caused by a newly identified coronavirus,
should be considered in travelers returning from Far East destinations or areas with known
prior SARS transmission (72,73). However, the last reported cases occurred in China in 2004
[CDC SARS situation report]. SARS generally presents as a severe atypical pneumonia.
However, one proposed diagnostic algorithm among cases confirmed with RT-PCR was
associated with 90% sensitivity and 62% specificity (74). Predictors of SARS included:
(1) potential contact with a SARS patient; (2) an illness consisting of fever, myalgias, and malaise;
(3) an abnormal chest radiograph (diffuse haziness or consolidation); and (4) lymphopenia and
thrombocytopenia. Age>65 years or<18 years, sputum production, abdominal pain, sore
throat, rhinorrhea, and leukocytosis were not predictive of SARS. This tool was applied in one
epidemic setting and requires further validation (74–76).
The highly pathogenic avian influenza A (H5N1) has become the subject of much
international attention. The first reports of human disease appeared in 1997 and the incidence
has subsequently increased. The WHO reports that from 2003–2008 a total of 387 human cases
(245 fatal) were documented (77). Thus far, human to human transmission is exceedingly rare.
However, concerns for a viral mutation that would promote more effective transmission
among humans has prompted reassessment of pandemic influenza response plans and the
stockpiling of antiviral therapy as well as a recently FDA-approved H5N1 vaccine (78).
Optimal treatment of H5N1 influenza has yet to be determined. However, the WHO currently
recommends weight-based oseltamivir (75 mg po bid if>40 kg) for five days (79).
Coma and Meningoencephalitis
Infections may result in CNS dysfunction either indirectly as a systemic infection as in typhoid
fever or directly through CNS invasion. A returning traveler presenting with one or more of
328 Wood-Morris et al.