Background
Trench fever is a clinical syndrome caused by infection with Bartonella quintana. The condition was first described during World War I, when it affected nearly one million soldiers.[1, 2, 3, 4] It has been known by several different names, including quintan fever, shin bone fever, tibialgic fever, Wolhynia fever, and His-Werner disease. Similar illnesses have affected mankind throughout history.[5, 6]
Recent DNA studies have demonstrated that many soldiers in Napoleon’s Grand Army at Vilnius in the 19th century were infected with B quintana. In addition, B quintana DNA was found in a 4000-year-old human tooth in Roaix, France.[7, 8] Reports of trench fever outbreaks stopped after World War I and then reappeared transiently on the Eastern Front in Europe during World War II.
By the end of World War I, the human body louse Pediculus humanus was recognized as the most likely vector involved in trench fever transmission.[3, 4] Rickettsia -like bodies in the arthropod's body and feces were postulated to be the cause of the disease. In 1969, Vinson and coworkers reported successfully cultivating the causative organism (then called Rickettsia quintana) from a patient the trench fever and then reproducing the clinical disease by inoculating volunteers with the organism.[9] The organism was briefly placed in the genus Rochalimaea before being reclassified as Bartonella quintana in 1993. See the image below.
This illustration depicts a dorsal view of a female body louse, Pediculus humanus var. corporis. The human body louse P humanus var. corporis is a known vector responsible for the transmission of epidemic typhus, trench fever, and Asiatic relapsing fever. It also causes a dermatitic condition known as pediculosis. Courtesy of the CDC. At the time, trench fever was characterized by the abrupt onset of fever, malaise, myalgias, headache, transient macular rash of the torso, pain in the long bones of the leg (shins), and splenomegaly.[10, 6, 3, 4, 1, 2, 11, 12] Typical periodic cycles of fever, chills, and sweats occurred at 5-day intervals, resulting in prolonged disability that lasted 3 months or longer in young soldiers. However, no cases of mortality attributable to trench fever were recognized.
Bartonella species emerged as a cause of bacteremia, angioproliferative disease (bacillary angiomatosis, parenchymal peliosis), and endocarditis in patients with and without HIV-related disease over the past 3 decades. In 1995, B quintana was recognized as a cause of bacteremia in 10 homeless alcoholic persons without HIV infection.[13] This was followed by a description of 3 HIV-negative, homeless, alcoholic males with endocarditis in France.[14] These cases suggested that B quintana –induced disease was not limited to wartime outbreaks or immunocompromised persons.
Subsequently, sporadic cases and small clusters of B quintana infection were described worldwide, associated with poor sanitation, poor hygiene, alcoholism, and malnutrition, all factors that are common to war, famine, homelessness, and poverty. Seroprevalence studies suggest that B quintana infection is more common than clinically recognized and that many infections are subclinical.
The term urban trench fever is applied to contemporary B quintana disease. Urban trench fever is typically found in homeless, alcoholic, and poverty-stricken populations in whom poor personal hygiene is common. The infection affects both immunocompetent and immunocompromised persons. Some (but not all) persons with urban trench fever have evidence of external parasitic infestation.
The spectrum of disease associated with B quintana infection includes asymptomatic infection, urban trench fever, angioproliferative disease, chronic lymphadenopathy, bacteremia, and endocarditis.[6, 15, 16]
Pathophysiology
After introduction into the human body, Bartonella bacteria invade erythrocytes and endothelial cells, where the organism proliferates.[17] Intraerythrocytic B quintana colonization is largely limited to human beings.[6, 15] Invasion of vascular endothelial cells is less species-specific and has been shown to occur in several mammalian cell lines in vitro.[18]
Investigation of the pathogenetic mechanisms of Bartonellabacteria is centered on the relationship between erythrocytes and targeted vascular endothelial cells. Once the organism invades and begins to multiply within the endothelial tissues, proinflammatory cytokines are activated, apoptosis is suppressed, and vascular proliferation occurs.[19] These changes result in systemic symptoms (fever, chills, sweats), bacteremia, vascular proliferation, intravascular infection, and lymphatic enlargement. The lipopolysaccharide of B quintana is also a natural antagonist of Toll-like receptor 4.[20]
Another species, Bartonella henselae, is known to produce the same lesions (although seemingly more extensive) in immunocompromised adults. B henselae is the only Bartonella species known to cause parenchymal (hepatic) peliosis.[6] Bacillary angiomatosis resembles the verruga peruana caused by Bartonella bacilliformis,[21] which seems to stimulate production of angiopoetin-2 and vascular endothelial growth factor.[22] The relationship between the endothelial vascular proliferation and the destructive valvular lesions of B quintana endocarditis is unknown. The histologic features of these two clinical variants differ.[6]
The pathogenesis of B quintana –associated disease suggests that bacteremia is an early occurrence in all the various syndromes attributed to this organism. It lasts for a few days in some patients, while it lasts months to years in others.[15] B quintana exists inside erythrocytes, where it is protected from the host's humoral immune response.[17] Monocytes from homeless individuals with chronic B quintana bacteremia have been shown to overproduce interleukin-10, resulting in an attenuated immune response that may explain the bacterial persistence.[23] This same group of patients generate a poor humoral antibody response than patients with endocarditis, in whom the inflammatory response is more dramatic and bacteremia less frequent.[24] Other pathogenetic mechanisms are unknown.
The clinical features of trench fever in young soldiers during World War I and World War II were fairly consistent. However, the more recent descriptions of urban trench fever in homeless alcoholic populations are less uniform. B quintana endocarditis, bacillary angiomatosis, and chronic lymphadenopathy represent distinct syndromes that were unknown to the previous generations of military physicians. Whether these differences are due to gaps in medical knowledge, improved diagnostic techniques, host diversity, environmental changes, or variances in the genetic makeup of B quintana is unknown.
Epidemiology
Frequency
United States
The true incidence of urban trench fever is unknown. The disease occurs sporadically and in small clusters of homeless persons. A study found that 20% of the patients in a downtown Seattle clinic that serves a homeless indigent population had microimmunofluorescent antibody titers of 1:64 or greater to Bartonella species.[25] Multivariant analysis of these patients revealed that alcohol abuse was the only independent variable associated with seropositivity. Most of these patients were asymptomatic.
International
B quintana –related illness has been found on every continent except Antarctica. Well-performed seroprevalence studies have revealed patients with B quintana antibodies in France, Greece, Sweden, Japan, Brazil, and Peru.[24, 26, 27, 28, 29, 30] Cases of culture-negative endocarditis with antibody titers positive for B quintana have been reported in Europe, Australia, Japan, Tunisia, and India.[31, 32, 33, 34, 35]
Mortality/Morbidity
During World War I, trench fever resulted in significant morbidity and prolonged disability, but no recognized mortality. Contemporary descriptions of B quintana endocarditis in homeless alcoholic males resulted in a mortality rate of up to 12%, related to complications of endocarditis or to the surgery used in its treatment.[36, 37]
Race
No convincing data suggest that urban trench fever or other syndromes caused by B quintana infection have a racial or ethnic predilection.
Sex
Historically, trench fever was an infection of soldiers in World War I and World War II; therefore, most documented cases were in males. Descriptions of urban trench fever described since 1995 have predominantly involved males, reflecting the disproportionate representation of males in the homeless alcoholic population.
Age
Cases of trench fever described during wartime typically affected young soldiers. In contrast, urban trench fever typically affects middle-aged adults. Rare cases of Bartonella endocarditis and CNS infection have been described in children.
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