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716 PART 5: Infectious Disorders

gas exchange, avoidance of intubation, and less associated ventilator- and Drug Administration but is available with the Centers for Disease
associated pneumonia. However, intubation remained high in patients Control, and arrival of artesunate can occur quickly in many situations.
when illness was more severe (Simplified Acute Physiology Score II If a long delay occurs (ie, more than 12 hours), quinidine should be
<175), sug- used. Artesunate has few side effects, with a decline in reticulocyte count
>35) or hypoxemia did not improve after 1 hour (Pa O 2 /Fi O 2
gesting that NPPV may be useful in early ARDS in less severe patients being the most common. Additional support with blood transfusions
who respond quickly. 21,26 With the SARS experience in Canada, NPPV can be considered in cases of altered consciousness, high output heart
was also associated with an increased risk of disease transmission. This failure, respiratory distress, and/or high density parasitemia. Exchange
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experience was based largely on case studies and was not reported with transfusion is additionally an option to reduce parasite load. Blood
SARS cases in Asia. Thus, the likelihood of increased disease transmis- transfusion and exchange transfusion are largely supportive and have
sion with NPPV use in a febrile critically ill traveler can increase disease not been shown to reduce mortality. Thus they should not delay the
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transmission. 23,26-28 In summary, the use of NPPV with an infected ARDS onset of therapy with artesunate or quinine. In rare cases, non-falciparum
patient remains controversial, with some benefit possible in less severe, malaria can cause severe disease, and in these cases, treatment is identical
early ARDS cases that can potentially increase disease transmission. to falciparum therapy with artesunate or quinidine.
■ EMPIRIC THERAPY IN THE TRAVELER

Figure 77-1 outlines the approach to a critically ill traveler with initial INFLUENZA
diagnostics and respiratory isolation. Severe malaria, rickettsial disease ■ SEASONAL INFLUENZA
with multiorgan failure, and bacterial sepsis with multiorgan failure
(meningococcus, plague, tularemia) can respond to early antimicrobial An acute respiratory illness can be caused by either influenza A or B,
therapy. For viral syndromes such as MERS-CoV, VHF, and dengue, usually as an epidemic during the winter season. Influenza A viruses
supportive care is essential. For influenza, however, therapy with a neur- are usually of the H1 and H3 subtype, which differs from the avian
aminidase inhibitor is essential in the first 48 hours. Therefore, empiric influenza A subtypes (ie, H5N1) seen recently. 23,24 However, the H1N1
therapy with an antimalarial, specifically artesunate or quinine, should pandemic of 2009 highlighted the severe number of cases that can occur
be initiated while diagnostic testing is pending. 18,29 The administration with influenza. 36,37 Most cases are self-limiting infections with systemic
of doxycycline for rickettsial disease should occur along with a broad- illness such as fever, headache, myalgias, and malaise (an influenza-like
spectrum antibacterial, such as ceftriaxone, ampicillin-sulbactam, or illness [ILI]). 38-41 However, a smaller number of individuals, particularly
imipenem. 18,29 Finally, for patients traveling to areas of active influenza higher risk individuals are more likely to develop a primary pneumonia,
(winter months), oseltamivir should be initiated. 23 and in cases of H1N1 of 2009, many health individuals progressed to
severe disease. 36,37 Diagnosis is by viral detection in lung and nasal wash
samples in a patient with appropriate clinical symptoms, with subtyping
SPECIFIC DISEASES AND THERAPY done by polymerase chain reaction in public health laboratories.
■ MALARIA the presence of comorbidities. Prompt initiation of antiviral therapy
The treatment of influenza is dependent on the severity of illness and
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Malaria is the most classic disease associated with travel and is endemic for individuals with suspected or confirmed influenza infection should
throughout most of the tropics. Over 243 million will develop symptom- occur in the following settings: (1) severe or complicated illness requir-
atic malaria annually, with most of these cases being attributable to P ing hospitalization, regardless of previous health or vaccination status,
falciparum (90%), but P vivax and P knowlesi can also cause symptomatic (2) age ≥65 years, (3) pregnant women and women up to 2 weeks post-
disease. Indeed, P vivax, P ovale, and P malariae have been associated partum, (4) high-risk individuals including immunosuppression, under-
30
with severe disease in some rare cases. Severe malaria is defined as a para- lying lung disease, heart disease, obesity, and malignancy. 36,37 All patients
sitemia of 5% to 10% of red blood cells (5% in low incidence regions and with these risk factors, including those with mild illness not requiring
10% in high incidence regions) with signs of end organ damage: altered hospitalization, should be treated with antiviral therapy. Adults with
consciousness with or without seizures, respiratory distress or ARDS, mild illness without high-risk conditions who are younger than 65 years
hypotension and heart failure, metabolic acidosis, renal failure with of age do not require treatment unless they have severe or complicated
hemoglobinuria (“blackwater fever”), hepatic failure, coagulopathy, severe disease neuraminidase inhibitor.
anemia, and hypoglycemia. Cerebral malaria with encephalopathy and Antiviral therapy with a neuraminidase can shorten the duration of
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seizures carries the worst prognosis. Severe malaria requires rapid treat- influenza symptoms by 1 to 3 days when initiated within 48 hours of
ment due to the potential for rapid decline and death within 24 hours of symptom onset in individuals at low risk. 36,37 The benefit has been greatest
onset, and as such, therapy should be initiated when suspected. 31,32 when given within the first 24 to 30 hours and in patients with fever at
The clinical manifestations of severe malaria vary with age, species, presentation. Studies from the H1N1 pandemic suggested that antiviral
and geography. Young children (ages 2-5 years) and pregnant women are therapy reduced the severity and incidence of complications of influenza,
at high risk for severe malaria. 31,32 Older children and adults develop par- the duration of hospitalization in patients with severe influenza, and
tial immunity to febrile malaria episodes (but not to malaria infection) influenza-associated mortality in patients at higher risk, including hos-
after repeated infection, and thus are at relatively low risk for severe pitalized individuals. As with the initial neuraminidase studies, initiation
disease. Travelers to areas where malaria is endemic generally have no within 48 hours of symptom onset had the greatest mortality benefit. 36,37
previous exposure to malaria and thus are at high risk for progression to Given that timing is important, therapy should be initiated immediately
severe disease, particularly with P falciparum. For this reason, malaria is in all cases of suspected or proven severe influenza. Therapy should not
an extremely important consideration in all travelers with severe disease. be delayed for testing results, and prior vaccination should not alter the
Parenteral therapy is preferred for rapid treatment. 31,32 There are two initiation of therapy when influenza is circulating in the community. 38-41
major classes of drugs available by IV administration: the cinchona Influenza should be suspected during the winter epidemic season or if
alkaloids (quinine and quinidine) and the artemisinin derivatives (arte- travel to an endemic area has occurred. 23,24 Spread is by droplet transmis-
sunate, artemether, and artemotil). 31-35 Based on clinical trials, artesunate sion and contact with respiratory secretions, so patients suspected with
is superior for treatment of severe falciparum malaria when compared influenza should be placed in droplet isolation and HCWs should wear
to quinine. 31-35 If artesunate is not available, quinine (or quinidine in the surgical masks, face shields, eye protection, gowns, and gloves as the
United States) remains the drug of choice. Artesunate is not yet available appropriate personal protective equipment (PPE). 23,24 Based on the SARS
in many countries, thus, quinine remains the treatment of choice in those experience, higher risk procedures generating aerosols may require the
instances. In the United States, artesunate is not approved by the Food use of an N-95 mask or a powered air purified respirator (PAPR). 23,24

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