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720 PART 5: Infectious Disorders

Pneumonic tularemia occurs with primary inhalation or hematogenous created a foundation of early isolation and enhanced PPE when engaging
spread from typhoidal tularemia and this is felt to be the main clinical in certain higher risk procedures. 26,108 The epidemic waned without fur-
presentation in a bioterrorism event with tularemia. 95,98 The incuba- ther cases being reported, so detection based on clinical grounds would
tion period tends to be shorter in these cases, with the rapid onset of require a high level of suspicion. Therefore, any consideration of SARS or
pneumonia developing. Radiographic studies show patchy infiltrates another potential virus should promptly be reported to hospital infection
bilaterally, lobar disease, and hilar adenopathy. 99,100 Pleural effusions control and the public health official. 26,108
and a military pattern can also occur, although this is less common.
Respiratory failure and ARDS develop quickly. 94,95 Typhoidal tularemia ■ MERS-CoV
is rare and can occur with or without pneumonia, as patients present
with a febrile illness followed by sepsis without the glandular disease. Middle East respiratory syndrome coronavirus (MERS-CoV) is a beta-
Oropharyngeal tularemia occurs rarely when undercooked infected coronavirus, different from the other human betacoronaviruses (severe
meat or water is ingested and is associated with fever, pharyngitis, and acute respiratory syndrome coronavirus), but closely related to several
109,110
cervical lymphadenopathy. 94,95 Oculoglandular tularemia occurs with bat coronaviruses. In September 2012, a case of novel coronavirus
direct inoculation from contaminated fingers or accidental exposure. infection was reported involving a man in Saudi Arabia who was admit-
Besides conjunctival swelling and erythema, regional lymphadenopathy ted to a hospital with pneumonia and acute kidney injury in June of
111,112
may be present. 94,95,99,100 Francisella tularensis is very difficult to grow on the same year. This was the first sign of this novel virus, and to
culture media (requires cysteine), and since it is largely an intracellular date, over 190 cases have been detected in over six Middle East coun-
organism, diagnosis is difficult. 95,101,102 Clinical suspicion must be high, tries, most notably Saudi Arabia. Cases have also been reported from
particularly if the risk factors of vector exposure, animal exposure, or Tunisia, Germany, United Kingdom, France, Italy, and Spain. In all five
multiple community cases suggesting aerosolization occur. Therefore, European countries and Tunisia, a patient developed illness after return-
serology by ELISA or histologic examination showing gram-negative ing from the Middle East. In the United Kingdom, France, Italy, and
intracellular organisms is the most likely method. 95,101,102 If serology is Tunisia, limited human-to-human transmission occurred among close
111,112
performed, a single elevated titer may not be specific and thus acute contacts of the index cases. MERS-CoV is thought to be of animal
109,110
and convalescent titers are more predictive. For meningitis, chloram- origin and appears to be related to several bat coronaviruses. Some
phenicol is preferred. 94,95 The overall mortality for tularemia is around infections most likely have occurred via intermittent zoonotic trans-
4%, but felt to be higher in aerosolized disease that causes pneumonia mission or possibly via an environmental source. The presence of case
or typhoidal tularemia. 95,101,102 Particular ICU management of tularemia clusters strongly suggests that human-to-human transmission occurs.
includes supportive care and low-tidal-volume ventilation for ARDS. For epidemiologic purposes, the following case definitions have been
19
Human-to-human transmission does not occur, so once the diagnosis proposed by the World Health Organization: Confirmed case is a person
is confirmed, respiratory isolation can be lifted. Tularemia is a zoonosis, with laboratory confirmation of infection with MERS-CoV. Probable
so prevention is largely vector and exposure avoidance. 94,95 Prophylaxis case is a person with an acute respiratory infection (with or without
is not needed for human exposures but is indicated for aerosol exposure fever) with clinical, radiographic, or histopathologic evidence of pulmo-
in an outbreak or bioterrorism event as well as in a laboratory worker nary parenchymal disease (eg, pneumonia or ARDS) and inability to per-
exposure. Reporting tularemia to public health officials varies across form laboratory testing or a close contact with a laboratory-confirmed
North America, but pneumonic or typhoidal cases, particularly if felt to case. The incubation period is 2 to 14 days after initial exposure as
109,110
be secondary to a bioterrorism event, should be reported. 94,95 defined by the case clusters. The main clinical findings include
fever (>38°C) (98%), cough (83%), shortness of breath (34%), phar-
yngitis (21%), hemoptysis (17%), GI symptoms (15%), abdominal pain
ACUTE RESPIRATORY FAILURE (17%), and abnormal chest radiographs (100%). 109,110 Most patients
■ SARS with MERS-CoV infection have been severely ill with pneumonia and
ARDS, and some have had acute kidney injury. Over 89% require an
113
SARS is caused by a novel coronavirus (SARS-CoV) that was first ICU admission and 75% require mechanical ventilation. Some have
113
detected in 2003. Although it has not recurred, the addition of a new progressed to need extracorporeal membrane oxygenation. Other than
27
coronavirus in the Middle East, MERS-CoV, highlights the importance abnormal chest radiographs, laboratory findings are less specific. 109,110
of this class of viruses to travelers. SARS can serve as a template for The diagnosis is made by serology or DNA-based testing, but these are
detection and management. Thousands of cases occurred worldwide in only performed at specialized laboratories in the public health system.
the initial epidemic in 2003, but the epidemic abated and new cases have Any suspected case should prompt an immediate call to the public health
not been reported since. 26,28,103-105 The clinical presentation is character- department along with rapid isolation in a negative pressure facility or
ized by fever, chills, rigors, malaise, nausea, and shortness of breath. The room. 114-116 Treatment is supportive, with lung-protective strategies for
symptoms occurred on average 7 days after contact. Pneumonia develops mechanical ventilation providing the biggest backbone of treatment. 109,110
approximately 8 days after onset of fever, with 45% of patients developing Combination therapy with interferon (IFN)-alpha-2b and ribavirin
hypoxia. 26,28,103-105 About 20% of patients then develop ARDS and require appears promising but remains experimental. 114-116 Due to the emerging
mechanical ventilation. Development of ARDS form onset of fever is nature of this disease, along with potential high level of contagiousness,
28
bimodal, with peaks at 11 and 20 days. 26,28,103-105 The global fatality rate travelers from the Middle East should be evaluated for MERS-CoV when
was 11% with most cases over age 65. No deaths were reported in chil- presenting with ARDS and critical illness.
dren. Diagnosis includes an influenza-like illness with severe pneumonia
in the presence of the epidemic with viral isolation by PCR in respira- THE IMPACT ON PUBLIC HEALTH AND COMMUNITY
tory samples. 26,28,103-105 A serum immunofluorescence assay may detect
cases long after onset. Treatment is largely supportive, but steroids were In most cases, the etiology of a febrile illness in a critically ill traveler is
used in some cases that progressed to ARDS. Initial cases in 2003 were largely unknown upon admission to the ICU. While bacterial pathogens
difficult to identify, which led to spread extensively to HCWs. Spread constitute most cases, the breadth of agents that can cause disease is
103
is by droplet transmission, although many cases suggest that airborne enormous, with many having direct impacts on public health systems
and contact routes also occur. 106,107 Spread to HCWs who wore appro- and the community. Many of these cases require further epidemiologi-
priate personal PPE suggests airborne spread, and additional spread by cal and diagnostic testing, which can take time and resources in order
aerosol-generating procedures such as resuscitation (CPR), medication to determine the larger impact of one critically ill traveler. Often these
nebulization, and noninvasive ventilation further supports this method patients will not be isolated and tested for these pathogens upon
of spread. 23,24 The experience with SARS, particularly among HCWs, has admission, and they will additionally undergo higher risk aerosolizing

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