Page 988 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 77: Management of the Critically Ill Traveler 719

7 days after exposure. 78,80,81 Classic symptoms of RMSF include fever, found largely in the western states. The most recent outbreaks in 1992
88
headache, and rash in a person with a history of a tick bite. However, occurred in Africa, South America, and Asia. Three recognized clinical
all of these diagnostic clues are rarely identified on the initial patient syndromes are associated with plague: bubonic plague (80%-90% of
encounter, leading to delays in appropriate therapy. In fulminant cases cases), septicemic plague (10% of cases), and pneumonic plague (very
of RMSF, death may occur in as early as 5 days. Poor outcomes have rare). 85,87 After an incubation of 2 to 7 days, clinical symptoms usu-
been associated with delay of appropriate antibiotics. In the early phase ally occur and differ depending on clinical syndromes. 85,87 In bubonic
of illness, most patients have nonspecific signs and symptoms, such as plague, a sudden onset of fevers, chills, and headache is followed by
fever headache, malaise, myalgias, and arthralgias. 78,80,81 Rash occurs intense pain and swelling in the regional lymph nodes proximal to the
in approximately 88% to 90% of patients between the third and fifth site of the bite or scratch. This lymph node, or bubo, is characterized
days of illness. The hallmark of RMSF is a blanching erythematous by intense tenderness with erythema and edema but without fluctua-
rash with macules (1-4 mm in size) that become petechial over time. In tion. Without treatment, disease disseminates leading to complications
severe cases, the rash may become confluent, with some areas of skin such as pneumonia, meningitis, sepsis, and multiorgan failure. The
91
undergoing necrosis due to pathogen-induced damage. 78,80,81 A potential development of a secondary pneumonia becomes extremely concerning
diagnostic problem is that rash never occurs in up to 10% of patients. as these patients are highly contagious. With septicemic plague, acute
These cases of “spotless” RMSF may be severe with a fatal outcome. In fever followed by sepsis without the presence of a bubo. Additional
addition, the rash can be easily overlooked in dark-skinned individuals. gastrointestinal symptoms such as nausea, vomiting, and diarrhea are
Thus, the absence of a rash, or tick bite, should not limit treatment in the also known to complicate septicemic plague. 85,87,92 Rapid sepsis, dis-
critically ill traveler. Major complications include encephalitis, noncar- seminated intravascular coagulation, and multiorgan failure develop
82
diogenic pulmonary edema, ARDS, cardiac arrhythmias, coagulopathy, quickly after the inoculating flea bite. In pneumonic plague, most cases
gastrointestinal bleeding, and skin necrosis. The onset of neurologic are secondary from bubonic or septicemic plague, but a primary pneu-
involvement is associated with increased risk of mortality and morbid- monic plague can occur after exposure to infected humans, animals, or
ity. The cases with neurologic findings and shock are often the most aerosols in an intentional bioterror attack. 85,87,92 Due to the high conta-
83
critical and progress to death rapidly. giousness of plague, disease can spread rapidly with primary pneumonia
Most patients with RMSF have a normal white blood cell count at as seen with past outbreaks in human history, subsequently creating
presentation. As the illness progresses, thrombocytopenia becomes a sustained pandemic. Initial cases in primary pneumonic plague have a
82
more prevalent and may be severe and this is a helpful diagnostic clue very short incubation period of hours to a few days, followed by sudden
to the possibility of rickettsial disease. Other findings in advanced onset of fever, cough, rapid onset of respiratory failure and ARDS, and
84
cases include hyponatremia, elevations in serum aminotransferases and death. 85,87,92 Diagnosis is primarily by culture of the sputum or blood as
bilirubin, azotemia, and prolongation of the partial thromboplastin and Yersinia pestis grows well on most laboratory media. 85,87,92 Serology and
prothrombin times. Hyponatremia is a particularly common finding in rapid diagnostic testing by ELISA or PCR is also available but is used
patients with central nervous system involvement. The cerebrospinal primarily in field testing. Traditionally, treatment has been streptomy-
fluid analysis may demonstrate pleocytosis of both monocytic and cin, but based on its limited availability, gentamicin or doxycycline now
polymorphonuclear predominance. The diagnosis of RMSF is initially is preferred. 85,87,92 Chloramphenicol is preferred for cases of meningitis
82
made empirically based on consistent clinical symptoms and signs in due to its ability to cross the blood brain barrier. Pneumonic plague
93
the appropriate epidemiologic setting. The clinical diagnosis must be and septicemic plague in the ICU will have multiorgan failure with
84
confirmed by skin biopsy or through serologic testing. Early therapy for ARDS, so management should include a protective lung strategy with
RMSF is important since a delay in treatment has been associated with low-tidal-volume ventilation and appropriate supportive care. Due to
an increased risk of mortality. Orally or intravenously administered dox- the high rate of transmission of plague via aerosols, all patients should
ycycline is the drug of choice for the treatment of RMSF in both adults be on strict airborne isolation until at least 48 hours of antibiotics have
and children, except for pregnant women, in which chloramphenicol is been given. Appropriate PPE, including an N-95 mask or PAPR, should
preferred. Antimicrobial therapy has had a dramatic effect on the case be worn and any exposure by an HCW should receive prophylaxis with
fatality rate of patients with RMSF as very few deaths are seen with doxycycline, chloramphenicol, or trimethoprim-sulfamethoxazole. 85,87,92
early, appropriate therapy. 78,80,81 Given the profound importance of early
therapy that can be altered with the difficulty of recognition and diag- ■ TULAREMIA
nosis, empiric doxycycline is recommended for all critically ill travelers Tularemia is caused by the gram-negative bacterium Francisella tula-
returning from endemic areas. 83 rensis and is a zoonotic disease, with humans as accidental hosts. 94,95
Francisella tularensis is found throughout the northern hemisphere
ULCER NODE SYNDROMES and in a wide variety of wild and domesticated species. The organism
■ PLAGUE persists in nature since it is passed transovarially in ticks, with disease
coming after bites from infected vectors (ticks, flies, mosquitos).
96,97
Yersinia pestis is the etiologic agent of plague and has caused a number of Susceptibility varies by species with rabbits and rodents having particu-
pandemics throughout human history. Plague is a zoonosis, primarily larly severe disease with nearly 100% mortality. Human infections occur
85
affecting rodents, with humans and other animals (domestic cats) being by vector contact (ticks and flies), handling infected animals, improperly
accidental hosts. The natural ecosystem of Yersinia pestis depends prepared animal meat, animal scratches and bites, drinking contami-
86
largely on the flea and rodent interaction, with seasonal variability nated water, or aerosolization of the organism from the environment
noted based on environmental conditions. Infected fleas bite their or in bioterrorism. 94-97 However, human-to-human transmission does
rodent hosts, inoculating the rodent. 85,87 Mortality in these animals not occur, largely since the organism is intracellular during infection
remains lower than other nonrodent mammals, and disease is passed and thus harder to spread from person to person. Approximately six
from infected rodent to flea and the life cycle continues. Transmission distinct clinical syndromes occur with tularemia: ulceroglandular, glan-
to humans occurs by rodent flea bites, infected animal scratches or dular, typhoidal, pneumonic, oropharyngeal, and oculoglandular. 95,98
bites, exposure to infected humans, and bioterrorism. 88,89 Transmission Ulceroglandular disease accounts for approximately 60% to 70% of
by infected flea bites is the most common mode, with squirrel, rabbit, disease. Abrupt onset of fevers, chills, headache, and malaise occurs
domestic cats, and prairie dogs being the most common animals of after an incubation period of 2 to 10 days. Most patients will have a
transmission. Large rodent or other animal die-offs, particularly in single papuloulcerative lesion with a central eschar and associated ten-
more susceptible species, may herald a large epidemic in nature. der lymphadenopathy. 95,98 In glandular disease, enlargement of lymph
90
Plague is found worldwide, and in the United States endemic disease is nodes occurs without the characteristic lesion (about 15% of cases).

section05_c74-81.indd 719 1/23/2015 12:37:33 PM