eMedicine Specialties > Infectious Diseases > Bacterial Infections

Trench Fever

Author: Alfred Scott Lea, MD, Associate Professor of Internal Medicine and Infectious Diseases, University of Texas Medical Branch School of Medicine
Contributor Information and Disclosures

Updated: Feb 20, 2009

Introduction

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.

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 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.¹¹ This was followed by a description of 3 HIV-negative, homeless, alcoholic males with endocarditis in France.¹² 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.^6,13

Pathophysiology

After introduction into the human body, Bartonella bacteria invade erythrocytes and endothelial cells, where the organism proliferates.¹⁴ Intraerythrocytic B quintana colonization is largely limited to human beings.^6,13 Invasion of vascular endothelial cells is less species-specific and has been shown to occur in several mammalian cell lines in vitro.¹⁵

Investigation of the pathogenetic mechanisms of Bartonella bacteria 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.¹⁶ 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 4.¹⁷

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,¹⁸ which seems to stimulate production of angiopoetin-2 and vascular endothelial growth factor.¹⁹ 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.¹³ B quintana exists inside erythrocytes, where it is protected from the host's humoral immune response.¹⁴ 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.²⁰ 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.²¹ 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.

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.²² 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.^{21,23,24,25,26,27} Cases of culture-negative endocarditis with antibody titers positive for B quintana have been reported in Europe, Australia, Japan, Tunisia, and India.^{28,29,30,31,32}

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.^33,34

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.

Clinical

History

Trench fever was recognized and precisely described as a distinct syndrome by several physicians during World War I.^10,1,2,3,4 The clinical incubation period seemed to be 3-48 days.³⁵ Associated infestation with lice was common. Young soldiers with trench fever would experience headache, relapsing fevers, shin pain, truncal rash, and splenomegaly. Most patients could remember vividly the specific time of symptom onset.

The differential diagnoses of the initial symptoms associated with trench fever included typhoid fever, epidemic typhus, influenza, and meningitis. While there was no recognized mortality, the disability it caused was prolonged and total.

Headaches were sudden in onset and were described as frontal or retroorbital. They were often associated with a stiff neck and photophobia, raising the possibility of meningitis. Other neurologic symptoms included weakness, depression, restlessness, giddiness, and insomnia. Many patients with trench fever would experience severe prostration that resulted in disability and the inability to get out of bed.

The onset of fever was also dramatic and coincided with the onset of headaches. Temperatures were often as high as 104ºF and were associated with malaise, chills, rigors, and sweats. Fever occurred in three distinct patterns. Abortive fever was described as a temperature elevation lasting several days, after which the fever abated and disappeared. Relapsing fever was the most commonly observed pattern and occurred at 5-day intervals (range, 4-8 d), leading to the names quintan fever and five-day fever. The fever would progressively increase during the first episode and then progressively improve during subsequent paroxysms. The third pattern was continuous fever, which lasted for the duration of the disease. Fever occurring months to years after the original defervescence were occasionally reported.

Bone pain, particularly involving the shins, progressively worsened throughout the duration of the illness. The pain worsened dramatically with exercise and was so severe that prostrate patients did not move in their beds because of the pain. Another similar symptom was loin pain, which radiated to the lower extremities or up into the back.

Gastrointestinal symptoms of trench fever would begin with diffuse abdominal pain, often associated with anorexia, nausea, vomiting, weight loss, diarrhea, and constipation. Conjunctivitis was another common initial symptom. An erythematous truncal rash and tachycardia would develop during the febrile episodes. The rapid heart rate worsened with exercise. Dyspnea was associated with the fever and tachycardia.

More recently, urban trench fever has been characterized by one or more of the described symptoms described above, but with less uniformity.^{6,36,28,11,13,33} Urban trench fever occurs in homeless and alcoholic persons who exhibit poor personal hygiene. The presence of lice and other external parasites is less prevalent in these individuals. Headaches, conjunctivitis, relapsing fever, and shin pain have been documented, while abdominal and neurologic symptoms appear to be uncommon.

The descriptions of other syndromes associated with B quintana infection over the last thirty years were unknown to physicians during World War I. A large percentage of persons with B quintana infection may be totally asymptomatic, and those with any of the identified syndromes may have negative blood culture results. Chronic lymphadenopathy typically manifests as enlarged cervical lymph nodes and no fever or other associated symptoms.⁶ Individuals with bacillary angiomatosis are asymptomatic and exhibit only the characteristic skin lesions, with or without regional lymphadenopathy.¹³ B quintana endocarditis manifests as fever, new murmurs, and heart failure and causes embolic phenomena in at least 20% of patients.³⁴ Chronic B quintana bacteremia is occasionally accompanied by all of the syndromes described above and may last for years.²¹

Physical

The physical findings of trench fever during World War I were fairly consistent. Infected persons experienced an abrupt onset of fever (up to 104ºF), associated with shivering, rigors, and diaphoresis. Patients would initially exhibit a toxic appearance associated with prostration. A furred or coated tongue was common. Some patients were able to continue with their daily activities and recover after a short fastigium, but most would develop a chronically ill appearance with obvious depression and significant disability for months. The fever patterns are described above (see History).

Patients with trench fever exhibited a characteristic blanching, erythematous, macular rash that typically started on the trunk and extend as far as the abdomen, neck, and proximal extremities. The rash accompanied fever and would recur with each febrile paroxysm. It was not pruritic, but coexisting body louse and scabies infestations frequently resulted in itching and excoriations.

The vast majority of patients with trench fever developed conjunctivitis at the illness onset. Photophobia was common. Paroxysmal tachycardia generally paralleled the fever and could be exacerbated with exercise. Splenomegaly was common in those with the more prolonged courses of illness. Bone and muscle tenderness accompanied the shin pain and became progressively more severe and debilitating as the disease progressed. Loss of the Achilles reflex was common.

The characteristic physical findings of urban trench fever are less typical. Rash, fever, conjunctivitis, bone tenderness, splenomegaly, and neurologic signs (eg, absent Achilles reflexes) have been documented, but their appearance seems to be variable and less prevalent than in the initial descriptions from World War I. Nonspecific findings such as weight loss and weakness have also been reported. Many patients with microbiologic or serologic evidence of B quintana infection are totally asymptomatic.

Patients with B quintana endocarditis present with fever and murmur. Lesions typically involve the left side of the heart, resulting in the systolic murmur of mitral insufficiency, the diastolic murmur of aortic insufficiency, or both. Right-sided cardiac involvement is unusual. Heart failure may occur, and embolic lesions develop in up to 20% of patients.³⁴

Patients with chronic lymphadenopathy usually have lymphatic involvement of the cervical and mediastinal lymph nodes. They do not experience fever and are otherwise asymptomatic.

Immunocompetent individuals with bacillary angiomatosis typically exhibit one or more papules that progress to nodules that may be confined to one or more anatomical regions. They may also be disseminated. The lesions are red, purple, or nonpigmented and can be superficial or subcutaneous. They may be mobile or fixed to underlying structures, such as bone, and bleed profusely when punctured or incised. Associated regional adenopathy is common. Patients are typically afebrile. The same lesions occurring in immunocompromised patients are generally more widespread and are more likely to involve visceral organs such as the liver, spleen, and GI tract.

Causes

B quintana causes both trench fever and urban trench fever.^6,9 Humans are the predominant reservoir of the pathogen, although infection has been shown in some subhuman primates and cats.^37,35,38,39 In infected persons, the organisms can be found in human blood, tissues (particularly skin), and urine.⁶

Predisposing factors for B quintana infection have included war, famine, malnutrition, homelessness, alcoholism, intravenous drug abuse, and poor hygiene.

Since B quintana bacteremia may be intermittent or prolonged for years, ingestion of organisms infecting human erythrocytes suggests that blood-sucking arthropods are efficient transmitters of B quintana infection.^14,13 External parasitic infestations are also associated with conditions of squalor. The body louse P humanus is the major vector for both trench fever and urban trench fever, but its presence is not always demonstrated in patients with urban trench fever.^9,12,40

Breaks in the skin contaminated by louse feces and arthropod bites are documented portals of entry. Other possible vectors include mites, ticks, and fleas.⁶ Contamination of mucous membranes, transfusion, transplantation, and intravenous drug abuse are also potential portals of entry. Human-to-human transmission of trench fever has not been well-described.

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