Download editorial rickettsia rickettsii: as virulent as ever

Am. J. Trop. Med. Hyg., 66(5), 2002, pp. 448–449
Copyright © 2002 by The American Society of Tropical Medicine and Hygiene
EDITORIAL
RICKETTSIA RICKETTSII: AS VIRULENT AS EVER
DAVID H. WALKER
Department of Pathology, University of Texas Medical Branch, Galveston, Texas
events, identification of rickettsial virulence genes), mechanisms of immunity (e.g., the role of dendritic cells and regional lymphatic spread and identification of host genes responsible for resistance and susceptibility), rickettsial antigens stimulating protective immunity, and interactions of
cytoplasmic rickettsiae with host cell signal transduction.6–8
However, few persons undertake the challenge of cultivating
these obligately intracellular bacteria in antibiotic-free systems in a biosafety level 3 environment or designing experiments that unravel the host cell and rickettsial effects in the
intracellular location.
Improvement in the case-fatality rate of RMSF requires
prompt consideration of the diagnosis in all febrile Dermacentor variabilis and Dermacentor andersoni tick-exposed patients in the United States and investigation of febrile patients
in Latin America, where the incidence and distribution of
Amblyomma cajennense- and Rhipicephalus sanguineustransmitted Rickettsia rickettsii as well as other rickettsioses
are undoubtedly underestimated.9,10 Perhaps the eventual
adoption of well-designed electronic medical records will lead
to automated prompting of physicians to inquire about potential tick exposure when fever is entered into the record
between May and September and to consider the diagnosis of
RMSF. Further, the use of a realistic case of RMSF in the
problem-based learning curriculum of all medical schools
would stimulate learning related to not only rickettsioses but
also many other important entities in the differential diagnosis. A reckoning of the plaintiff lawyer’s view of failure to
diagnose and treat fatal RMSF would be a sobering learning
experience for the students. Of course, the plaintiff lawyer is
wrong to consider the diagnosis of RMSF to be easy or to
expect all patients to recover from this deceptively difficultto-diagnose, highly virulent infection. However, the fact is
that a fatal outcome often ends up in a malpractice suit, a
situation that would be best avoided altogether.
There is room for more scientists in rickettsiology, and the
tools of molecular biology and cell biology allow more to be
accomplished. Medical science needs to develop better early
diagnostic tests (e.g., identification of the epitopes that stimulate the earliest detectable antibody response) and to provide
those tests that do exist (e.g., immunohistochemical detection
of rickettsiae in dermal endothelial cells) at least as referral
tests. However, in 2002, the best that can be achieved is the
appropriate empiric use of doxycycline except in cases involving pregnancy or known hypersensitivity. The less effective
antimicrobial agent, chloramphenicol, is an alternative, but
␤-lactams, aminoglycosides, macrolides, and sulfonamides
provide no benefit, as is repeatedly proven in fatal cases, in
which, inevitably, substantial quantities of one or more of
these antimicrobial agents were administered.
In their article on epidemiologic surveillance and risk factors for fatal Rocky Mountain spotted fever (RMSF), Childs
and Paddock provide scholarly insight into the history of public health epidemiology of an American infectious disease.1
The time frame spans from the period preceding knowledge
of the concept of infectious disease and of the rickettsial cause
of RMSF to the contemporary era.2 Their review of the previous analyses of risk factors for a fatal outcome of RMSF is
comprehensive and stimulates a series of questions: Why is
RMSF misdiagnosed? Why is the problem neglected, including in the tropics? What could be done to improve the situation?
The misdiagnosis of RMSF is a failing of American physicians and medical education. Too many family physicians,
pediatricians, internists, and even emergency physicians do
not consider the possibility of RMSF in a febrile patient with
any number of other systemic symptoms and potential tick
exposure. The absence of rash during the early days of illness,
presence of other symptoms (e.g., gastrointestinal), and lack
of physician inquiry or patient knowledge of tick exposure are
frequently the case rather than the textbook description of a
petechial rash involving the palms and soles as may occur in
the late state, particularly in the most severe cases.3 Often by
then it is too late. In some areas where nearly all physicians
recognize RMSF as endemic, many unreported cases are
likely treated early and successfully with doxycycline. Unfortunately, RMSF occurs throughout most of the United States,
and in many states physicians are less aware of the disease.
Patients die of RMSF without ever being diagnosed accurately.
Another problem is that the clinical laboratory, the usual
source of a timely definitive diagnosis of infectious diseases,
seldom offers effective assistance in the diagnosis of RMSF in
the acute stage. Serologic results generally reflect the absence
of antibodies detectable by the available assays at this time in
the course of illness.4 Diagnostic skin biopsy immunohistochemistry requires the presence of rash lesions and is seldom
performed except as a reference test. RMSF is a neglected
disease because its brutal effects are dispersed, hidden by
misdiagnosis, and often dismissed as easily treated.5 If all of
the RMSF cases in the United States for a single year were to
occur in an affluent suburb of Washington, DC, during 1
week, much attention would be paid. Moreover, old, unresolved problems do not receive the attention that new, interesting issues do. For instance, compare the efforts placed on
researching West Nile virus or hantavirus pulmonary syndrome with the application of medical science to RMSF. Only
a handful of molecular microbiologists, immunologists, and
experimental pathologists are actually working in the laboratory with spotted fever rickettsiae. The scientific issues are
actually very interesting, including elucidation of the pathogenic mechanisms (e.g., reactivation of rickettsial pathogenicity in the feeding tick, the effect of tick saliva on the early
Author’s address: David H. Walker, Department of Pathology, University of Texas Medical Branch, 301 University Boulevard,
448
RICKETTSIA RICKETTSII
Galveston, TX 77555-0609, Telephone: 409-772-2856, Fax: 409-7722500, E-mail: [email protected].
6.
REFERENCES
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fever: is there more to learn? Am J Trop Med Hyg 66: 450–457.
2. Harden VA, 1990. Rocky Mountain Spotted Fever: History of a
Twentieth-Century Disease. Baltimore, MD: Johns Hopkins
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3. Walker DH, 1995. Rocky Mountain spotted fever: a seasonal
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4. Walker DH, Bouyer DH, 2002. Rickettsia. Manual for Clinical
Microbiology. Eighth edition. Washington, DC: ASM Press. In
press.
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DB, Treadwell TA, Krebs JW, Clarke MJ, Holman RC, Olson
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