Emerging Infectious Diseases * Volume 2 * Number 2 April-June 1996
Emergence of Bartonella quintana Infection among Homeless
Bartonella quintana has episodically emerged as a cause of
infection among distinct and diverse populations during the 20th century.
The organism was first identified as an important human pathogen during
World War I when it caused epidemics of louse-borne trench fever that
affected an estimated 1 million troops in Europe (1, 2).
Trench fever was characterized by fever, rash, bone pain, and splenomegaly
and ranged in severity from a mild flulike illness to a more severe,
relapsing disease. B. quintana infections were rarely recognized
from the end of World War II until the 1980s when the organism reemerged
as an opportunistic pathogen among HIV-infected persons. In this
population, B. quintana has been identified as a cause of bacillary
angiomatosis, endocarditis, and bacteremia (3-5) and
has been isolated from AIDS patients in France (6) and
the United States (3-5).
In the 1990s, B. quintana has emerged among homeless persons in
North America and Europe. In 1993, the organism was isolated from the
blood specimens of 10 patients at a single hospital in Seattle,
Washington, within a 6-month period (7). These
patients had illnesses characterized by fever and persistent bacteremia.
Endocarditis developed in two patients, one of whom required a heart valve
replacement. All 10 patients had chronic alcoholism, eight were homeless,
and the six who were tested for HIV infection were HIV-negative. These six
were the first cases of invasive B. quintana infection among
HIV-negative persons reported in the United States. Results of a
case-control study indicated that the patients with Bartonella
bacteremia were more likely than controls (other hospitalized patients
from whom blood specimens were obtained at approximately the same time) to
be homeless (p = 0.001), to have a history of alcohol abuse (p
= 0.001), and to be nonwhite (p = 0.007). The isolates from the 10
patients were identical by polymerase chain reaction
restriction-fragment-length polymorphism testing, which further suggests
that the cases were epidemiologically linked. Patients’ characteristics
were obtained by retrospective medical record review, and at the time they
sought treatment, three patients reported a recent cat scratch, five had
scabies, and one had lice. More complete information, however, on
patients’ past exposures to animals and ectoparasites was not available.
In 1995, Drancourt and co-workers reported three cases of B.
quintana endocarditis among HIV-negative, homeless, alcoholic men in
France (8). One of the patients had reported contact
with a dog, and one had reported contact with dogs and cats; however, a
current or past history of infection with lice or scabies was not
documented for any of the patients. In 1995, Stein and Raoult also
reported serologic evidence of B. quintana infection in an
HIV-negative, homeless man from Marseilles, who had a relapsing febrile
illness and a history of louse infestation (9).
As a follow-up to the 1993 B. quintana outbreak in Seattle in
1994, we conducted a seroprevalence study of anti-Bartonella
antibodies among patients at a community clinic in the “skid row” section
of Seattle, which serves a primarily homeless and indigent population
(10). The median age of the 192 patients included in the study was 45
years, 156 (81%) of the 192 were male, and 126 (66%) were classified as
homeless. B. quintana IgG titers >= 64 were detected by an indirect
fluorescence antibody assay (11) in 39 (20%) of the
192 clinic patients. In contrast, only 4 (2%) of 199 banked blood
specimens from an age-matched and sex-matched comparison group of Seattle
volunteer blood donors had titers >=64 (p < 0.001). Among clinic
patients, seropositivity (titer >=64) was associated by univariate
analysis with older age, homelessness (relative risk [RR] 2.0; 95%
confidence interval [CI] 1.0-4.1), alcohol abuse (RR, 2.5; 95% CI
1.4-4.2), smoking (RR, 2.0; 95% CI 1.2 -3.4), and injection drug use (RR,
2.5; 95% CI 1.3-4.8). By multivariate analysis, only alcohol abuse
remained independently associated with seropositivity (odds ratio 3.3; 95%
CI 1.6-6.9), and of 39 seropositive patients, 21 (54%)had a history of
chronic alcoholism. Reliable data on past exposure to animals or
ectoparasites were also not available for patients in this study.
The study was limited by the well-described cross-reactivity of the
assay between Bartonella species (12, 13), and
most (62%) clinic patients with B. quintana >= 64 also had titers
>= 64 to B. henselae. It is, therefore, possible that some of the
seropositive patients may have been exposed to Bartonella species
other than B. quintana. These findings do, however, show that a
surprisingly high proportion of clinic patients without a history of
documented Bartonella infection had detectable anti-Bartonella
antibodies and may have been exposed to B. quintana.
Multiple factors, including those related to disease transmission, host
susceptibility, and ability to detect the organism, have likely
contributed to the emergence of B. quintana infection among the
homeless. Transmission of B. quintana from human to human by the
body louse, Pediculus humanus, has been experimentally documented
(1) and is believed to have been the predominant mode
of transmission of epidemic trench fever in World Wars I and II. Lice
reside primarily in the seams of clothing and are easily killed by
immersion in water 50°C or warmer (14), which
explains the propensity for louse-borne infections among displaced persons
or wartime troops. Although these reports of B. quintana infection
among homeless persons lack sufficient information to conclusively
determine the disease vector, louse-borne infection remains a plausible
hypothesis. Lice, however, have not been associated with bacillary
angiomatosis among AIDS patients, although exposure to cats (and,
therefore, possibly to fleas) has been associated with bacillary
angiomatosis and bacillary peliosis caused by Bartonella species
(15) and with cat-scratch disease caused by B.
henselae (16). Thus, it is possible that B.
quintana infection is spread among homeless persons by as yet
unidentified vectors or reservoirs.
Homeless persons are also at risk for non-vectorborne infectious
diseases. An increased risk for tuberculosis in this population is well
documented (17, 18), and outbreaks of meningococcal
disease (19, 20), pneumococcal disease
(21), and diphtheria (22, 23)
have been reported. It is likely that factors such as crowding, altered
immunity due to alcoholism or other co-existing health problems, and
inadequate or infrequent access to medical care affect the transmission
and spread of infectious diseases among the homeless. Previous studies
have shown that the clinical response to a standard inoculum of B.
quintana varies substantially in experimental study patients
(1); this variation indicates that host factors are
likely important determinants of the risk for clinical infection following
exposure to the organism.
Although cases of B. quintana bacteremia among homeless persons
have thus far been reported only from France and Seattle, Washington, the
problem is probably not confined to these locations. B. quintana is
a fastidious and slow-growing bacterium that generally requires special
culturing techniques for isolation (3-5,
24), and many clinical laboratories do not routinely
use blood culturing methods that are sensitive for isolating this
organism. Moreover, B. quintana infection can result in a broad
range of often nonspecific clinical manifestations (1,
3-5); therefore, case-patients evaluated for suspected bacteremia may
represent only a small proportion of infected persons, as suggested by the
results of the Seattle seroprevalence survey. To better define the
geographic distribution and prevalence of B. quintana infection
among homeless populations, a heightened awareness for this infection on
the part of clinicians and the use of appropriate culture techniques by
microbiology laboratories serving this population are needed. In addition,
more specific serologic tests would aid in the diagnosis and assessment of
the epidemiologic characteristics of B. quintana infections.
The optimal treatment regimen for HIV-negative patients with suspected
or confirmed B. quintana infection has not been established.
Minimal published data exist regarding antimicrobial therapy for this
infection, and in vitro susceptibility testing has provenunreliable
(25). Nonetheless, on the basis of limited data, we
believe it is reasonable to treat immunocompetent patients who have
uncomplicated B. quintana bacteremia with at least 14 days of oral
therapy with erythromycin, azithromycin, doxycycline, or tetracycline. In
the 1993 Seattle outbreak, most patients had a satisfactory response to
treatment with a beta-lactam agent followed by either erythromycin or
azithromycin for 14 days (7). Although the number of
patients identified with B. quintana endocarditis is small, most of
these patients have required cardiac valve replacement despite intravenous
antimicrobial therapy (5, 8,
26). Therefore, we recommend that patients with B.
quintana endocarditis receive a more prolonged course of at least 4 to
6 months of antimicrobial therapy and cardiac valve replacement if needed.
Further study is needed to determine the role of bactericidal agents, such
as third generation cephalosporins or quinolones, as monotherapy or in
combination with a bacteriostatic agent for treating invasive B.
Many aspects of the acquisition and pathogenesis of B. quintana
infections, and specifically B. quintana infections among the
homeless, are not well defined. Changes in the organism itself that have
led to increased virulence may in part account for its reemergence;
however, microbiologic data that can support or refute this hypothesis are
lacking (27). The absence of recently identified
cases in Seattle and in other areas with laboratories that use culture
techniques appropriate for isolating Bartonella species suggests an
episodic pattern of disease, with few or no cases occurring during
interepidemic periods. It seems clear, however, that this most recent
emergence of an old disease is related, at least in part, to societal
factors that have contributed to urban decay and the existence of large
homeless populations in our cities. As with other emerging infectious
diseases, further efforts to identify, evaluate, and control B.
quintana infections among homeless persons are challenges that will
require the coordinated effort of clinicians, microbiologists, and public
Lisa A. Jackson, M.D., M.P.H.*, and David H. Spach, M.D.†
*School of Public Health and Community Medicine, and the †Division
of Infectious Diseases and the Department of Medicine, University of
Washington, Seattle, Washington, USA
- Vinson JW, Varela G, Molina-Pasquel C. Trench fever. III. Induction
of clinical disease in volunteers inoculated with Rickettsia quintana
propagated on blood agar. Am J Trop Med Hyg 1969;18:713-22.
- Slater LN, Welch DF. Rochalimaea species (recently renamed
Bartonella). In: Mandell GL, Bennett JE, Dolin R, editors.
Principles and practice of infectious diseases, 4th ed. New York:
Churchill Livingstone, 1995:1741-7.
- Welch DF, Pickett DA, Slater LN, Steigerwalt AG, Brenner DJ.
Rochalimaea henselae sp. nov., a cause of septicemia, bacillary
angiomatosis, and parenchymal bacillary peliosis. J Clin Microbiol
- Koehler JE, Quinn FD, Berger TG, LeBoit PE, Tappero JW. Isolation of
Rochalimaea species from cutaneous and osseous lesions of
bacillary angiomatosis. N Engl J Med 1992;327:1625-31.
- Spach DH, Callis KP, Paauw DS, et al. Endocarditis caused by
Rochalimaea quintana in a patient infected with human
immunodeficiency virus. J Clin Microbiol 1993;31:692-4.
- Maurin M, Roux V, Stein A, Ferrier F, Viraben R, Raoult D. Isolation
and characterization by immunofluorescence, sodium dodecyl
sulfate-polyacrylamide gel electrophoresis, western blot, restriction
fragment length polymorphism-PCR, 16S rRNAgene sequencing, and
pulsed-field gel electrophoresis of Rochalimaea quintana
from a patient with bacillary angiomatosis. J Clin Microbiol
- Spach DH, Kanter AS, Dougherty MJ, et al.Bartonella (Rochalimaea)
quintana bacteremia in inner-city patients with chronic
alcoholism. N Engl J Med 1995;332:424-8.
- Drancourt M, Mainardi JL, Brouqui P, et al. Bartonella (Rochalimaea)
quintana endocarditis in three homeless men. N Engl J Med 1995;332:419-23.
- Stein A, Raoult D. Return of trench fever [letter]. Lancet
- Jackson LA, Spach DH, Kippen DA, Sugg NK, Regnery RL, Sayers MH,
Stamm WE. Seroprevalence to Bartonella quintana among patients at
a community clinic in downtown Seattle. J Infect Dis 1996;173:1023-6.
- Regnery RL, Olson JG, Perkins BA, Bibb W. Serologic response to “Rochalimaea
henselae” antigen in suspected cat scratch disease. Lancet 1992;339:1443-5.
- Waldvogel K, Regnery RL, Anderson BA, Caduff R, Caduff J, Nadal D.
Disseminated cat-scratch disease: detection of Rochalimaea henselae
in affected tissues. Eur J Pediatr 1994;153:23-7.
- Dalton MJ, Robinson LE, Cooper J, Regnery RL, Olson JG, Childs JE.
Use of Bartonella antigens for serologic diagnosis of cat-scratch
disease at a national referral center. Arch Intern Med 1995;155:1670-6.
- Elgart ML. Pediculosis. Dermat Clin 1990;8:219-28.
- Tappero JW, Mohle-Boetani J, Koehler JE, et al. The epidemiology of
bacillary angiomatosis and bacillary peliosis. JAMA 1993;269:770-5.
- Zangwill KM, Hamilton DH, Perkins BA, et al. Cat scratch disease in
Connecticut: epidemiology, risk factors, and evaluation of a new
diagnostic test. N Engl J Med 1993;329:8-13.
- Barnes PF, El-Hajj H, Preston-Martin S, et al. Transmission of
tuberculosis among the urban homeless. JAMA 1996;275:305-7.
- Nardell E. McInnis B, Thomas B, Weidhaus S. Exogenous reinfection
with tuberculosis in a shelter for the homeless. N Engl J Med
- Filice GA, Englender SJ, Jacobson JA, et al. Group A meningococcal
disease in skid rows: epidemiology and implications for control. Am J
Public Health 1984;74:253-4.
- Counts GW, Gregory DF, Spearman JG, et al. Group A meningococcal
disease in the U.S. Pacific Northwest: epidemiology, clinical features,
and effect of a vaccination control program. Rev Infect Dis
- DeMaria A Jr, Browne K, Berk SL, et al. An outbreak of type I
pneumococcal pneumonia in a men’s shelter. JAMA 1980;244:1446-9.
- Pedersen AHB, Spearman J, Tronca E, et al. Diphtheria on skid road,
Seattle, Washington, 1972-75. Public Health Rep 1977;92:336-42.
- Heath CW Jr, Zusman J. An outbreak of diphtheria among skid row men.
N Engl J Med 1962;267:809-12.
- Larson AM, Dougherty MJ, Nowowiejski DJ, Welch DF, Matar GM,
Swaminathan B, Coyle MB. Detection of Bartonella (Rochalimaea)
quintana by routine acridine orange staining of broth blood
cultures. J Clin Microbiol 1994;32:1492-6.
- Myers WF, Grossman DM, Wisseman CL. Antibiotic susceptibility
patterns in Rochalimaea quintana, the agent of trench fever.
Antimicrob Agents Chemother 1984;25:690-3.
- Spach DH, Kanter AS, Daniels NA, et al. Bartonella (Rochalimaea)
quintana species as a cause of culture-negative endocarditis. Clin
Infect Dis 1995;20:1044-7.
- Relman DA. Has trench fever returned? N Engl J Med 1995;332:463-4.
Go To EID Home Page
Created: Wednesday, April 17, 1996, 11:08:15 AM