AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Trench fever is a blood-borne infection caused by a fastidious, pleomorphic, aerobic, gram-negative bacillus. The organism that causes trench fever previously was classified as Rochalimaea quintana and now is classified as Bartonella quintana. Historically, the infection was referred to as trench fever, 5-day fever, quintan fever, shinbone fever, shank fever, His-Werner disease, and Wolhynia fever.

The first clinical description occurred during World War I (WWI), but the condition has probably caused human infection for centuries. Trench fever was considered the most prevalent disease among Allied troops serving in the trenches during WWI. After WWI, trench fever became dormant, until it reemerged as an epidemic on the eastern European front during World War II. Since WWII, classic trench fever has almost disappeared as a clinical entity.

Over the past decade, a contemporary B quintana infection emerged in various US cities and abroad and was dubbed urban trench fever. This disease primarily affects inner-city dwellers, chronic alcohol abusers, and political refugees. Seroprevalence data on these populations suggest that exposure is common and many infections are subclinical. Endocarditis is prominent in recent urban trench fever cases among homeless, inner-city dwellers.

Pathophysiology

Little is known about the pathophysiology of classic trench fever. Prolonged bacteremia is common, but where the organism resides in the body is uncertain. Biopsy of skin lesions does not show organisms, but it does show perivascular lymphocytic infiltrates with inflammatory cells. Excised valves show perforations and fibrinous vegetations.

Frequency

United States

True incidence is not known; however, incidence reportedly occurs in small clusters of homeless persons. In Seattle, 20% of the patients in a downtown clinic that serves an indigent and homeless population had a greater than 1:64 microimmunofluorescence titer to B quintana, although most of these patients did not have symptoms of B quintana infection.

International

Trench fever is endemic to Eastern Europe, Russia, North Africa, and probably China, but the occurrence rate is unknown.

Mortality/Morbidity

Trench fever may cause significant morbidity and prolonged disability, but no fatalities are attributed.

Race

No race predilection exists.

Sex

Historically, trench fever was an infection of WWI and WWII veterans; therefore, most documented cases are in males.

Age

No particular age pattern exists.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Trench fever can have diverse clinical presentations ranging from practically asymptomatic to a persistent fever lasting months. The incubation period is 5-20 days.

• Symptoms
• • Sudden onset of fever
  • Headache (retro-orbital pain)
  • Malaise
  • Arthralgia
  • Anorexia
  • Conjunctivitis
  • Splenomegaly
  • Transient malar rash
  • Bone pain - Tends to occur in the shins (ie, tibia), neck, and back; worsens during subsequent attacks
• The following 4 major fever patterns occur in patients infected with B quintana:
• Asymptomatic infection with 1 episode of fever
• Single febrile episode occurring for 3-5 days without recurrence
• Multiple recurrent episodes (3-8) of fever, each lasting 3-5 days
• Persistent fever lasting 2-6 weeks

Physical

The physical examination findings can vary based on the level of patient symptoms during infection. The main features include the following:

• Conjunctivitis
• Rash
• • Rash may occur, most commonly during the first fever episode.
  • It usually appears in groups of erythematous macules or papules measuring 1 cm or less.
  • Approximately 70-80% of patients present with a rash on the abdomen, chest, and back.
• Splenomegaly
• Mild hepatomegaly
• Tachycardia

Causes

The body louse, Pediculus humanus, transmits classic trench fever. No human-to-human transmission occurs. The disease is transmitted by inoculation of the organism in louse feces through a skin break or a louse bite. Humans are the only known reservoir for the louse, and the patient can remain asymptomatic and bacteremic with B quintana for up to several years. Epidemic and endemic infection can occur in conditions in which lice are prevalent (eg, homeless populations, refugee camps, war, natural disasters).

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Ebstein-Barr virus
AIDS

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Bartonella infection is difficult to diagnose in the laboratory. Inform the laboratory about suspicion of B quintana infection, so that personnel can perform the special culture methods required for isolation.
• Culture
• • Isolator tubes (lysis-centrifugation) improve the blood culture yield.
  • Stain BACTEC bottles after 1 week of incubation with acridine orange. If organisms are present, subculture them onto blood or chocolate agar and incubate them at 37°C in 5% CO₂ and high humidity for up to 4 weeks.
• Serology
• • Both enzyme-linked immunosorbent assay (ELISA) and immunofluorescent assay (IFA) are available but exhibit substantial cross-reactivity with other Bartonella species.
  • For serologic diagnosis, paired sera that are 4 or more weeks apart can confirm diagnosis.
• Polymerase chain reaction
• • Polymerase chain reaction (PCR) technology confirms diagnosis and now is available at the Centers for Disease Control and Prevention (CDC).
  • PCR is specific to all Bartonella species and strains.

Imaging Studies

• Obtain an echocardiogram to clarify suspicion of endocarditis.

Histologic Findings

Biopsy of skin lesions show perivascular lymphocytic infiltrates with some inflammatory cells, but without organisms present.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Antibiotics are the mainstay of treatment for trench fever.

• Controlled studies are lacking for antimicrobial treatment of trench fever. B quintana is susceptible to penicillin G, ampicillin, methicillin, cephalothin, tetracycline, chloramphenicol, rifampin, gentamicin, erythromycin, azithromycin, clarithromycin, and doxycycline in vitro.
• Limited available data recommend doxycycline, erythromycin, or azithromycin.
• Tetracyclines, as a class, cause a dramatic response with disappearance of associated symptoms and defervescence, usually in 1-2 days.
• Initially, treat patients diagnosed with B quintana endocarditis with parenteral therapy and then a longer duration of overall therapy (4-6 mo).
• Some authors advocate adding a bactericidal agent intravenously (eg, third-generation cephalosporin, aminoglycoside) for the first 2-3 weeks of therapy.
• In a recent trial, Foucault and coworkers reported that doxycycline in combination with gentamicin is effective in the eradication of B quintana bacteremia.

Surgical Care

Evaluate the patient for valve replacement surgery if diagnosis of endocarditis occurs.

Consultations

Infectious disease specialists

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.

Drug Category: Antibiotics

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

Drug Name	Ceftriaxone (Rocephin)
Description	Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Bactericidal and works by arrests bacterial growth by binding to one or more of the penicillin binding proteins.
Adult Dose	2.0 g IV qd
Pediatric Dose	50-75 mg/kg/d IV qd or divided q12h; not to exceed 4 g/d
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	More than 10% of the treated subjects, children in particular, develop hematological changes (eosinophilia, thrombocytosis, less frequently leucopenia); an increase of transaminases is not uncommon (5-7%); ceftriaxone causes reversible biliary pseudolithiasis mainly in young women and children (ie, "sludge" in the gallbladder), occasionally with colics; dose adjustment necessary in renal failure; other rare adverse effects include headaches, dizziness, nausea, vomiting, abdominal pains, reduction of the renal functions, vaginitis, etc; pain can occur at the site of injection; since ceftriaxone may suppress bilirubin from the protein binding, it could favor a bilirubin encephalopathy in neonates; avoid in predelivery/neonates

Drug Name	Gentamicin (Garamycin, Jenamicin)
Description	Aminoglycoside antibiotic for gram-negative coverage bacteria, including Pseudomonas species. Synergistic with beta-lactamse against enterococci. Interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits. Dosing regimens are numerous and are adjusted based on CrCl and changes in volume of distribution, as well as body space into which agent needs to distribute. Dose of gentamicin may be given IV/IM. Each regimen must be followed by at least trough level drawn on third or fourth dose, 0.5 h before dosing; may draw peak level 0.5 h after 30-min infusion. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.
Adult Dose	Serious infections and normal renal function: 3 mg/kg/dose IV q8h Loading dose: 1-2.5 mg/kg IV Maintenance dose: 1-1.5 mg/kg IV q8h Extended dosing regimen for life-threatening infections: 5 mg/kg/d IV divided q6-8h Follow each regimen by at least a trough level drawn 0.5 h prior to the fourth dose; may draw a peak level 0.5 h after 30-min infusion
Pediatric Dose	<5 years: 2.5 mg/kg/dose IV q8h >5 years: 1.5-2.5 mg/kg/dose IV q8h or 6-7.5 mg/kg/d divided q8h; not to exceed 300 mg/d; monitor as in adults
Contraindications	Documented hypersensitivity; non-dialysis–dependent renal insufficiency
Interactions	Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; because aminoglycosides enhance effects of neuromuscular blocking agents, prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Initial patient management may require inpatient stay, depending on the severity of illness.

Further Outpatient Care

• Most treatment can occur on an outpatient basis.

In/Out Patient Meds

• Administer antimicrobial therapy (see Medications)

Deterrence/Prevention

• Instruct patients to improve hygiene and living conditions if part of an at-risk population.

Complications

• Relapse after treatment
• Endocarditis

Prognosis

• Infection usually is self-limited in immunocompetent hosts. In immunocompromised hosts, infection tends to be more severe and has the potential for death.

Patient Education

• Educate patients about practicing good hygiene. Humans are the only known reservoir of the louse, and human-to-human transmission does not occur.
• Explain vector control of the body louse.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Special Concerns

• Pregnancy - Affects appropriate choice of antibiotics for treatment
• Pediatrics - Affects choice of antibiotics for treatment

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Bass JW, Vincent JM, Person DA. The expanding spectrum of Bartonella infections: I. Bartonellosis and trench fever. Pediatr Infect Dis J. Jan 1997;16(1):2-10. [Medline].
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• Dehio C. Molecular and cellular basis of bartonella pathogenesis. Annu Rev Microbiol. 2004;58:365-90.
• Drancourt M, Tran-Hung L, Courtin J. Bartonella quintana in a 4000-year-old human tooth. J Infect Dis. Feb 15 2005;191(4):607-11. [Medline].
• Foucault C, Raoult D, Brouqui P. Randomized open trial of gentamicin and doxycycline for eradication of Bartonella quintana from blood in patients with chronic bacteremia. Antimicrob Agents Chemother. Jul 2003;47(7):2204-7. [Medline].
• Gluckman SJ. Q fever and trench fever. Clin Dermatol. May-Jun 1996;14(3):283-7. [Medline].
• Hollingdale MR, Herrmann JE, Vinson JW. Enzyme immunoassay of antibody to Rochalimaea quintana: diagnosis of trench fever and serologic cross-reactions among other rickettsiae. J Infect Dis. May 1978;137(5):578-82. [Medline].
• Jackson LA, Spach DH. Emergence of Bartonella quintana infection among homeless persons. Emerg Infect Dis. 1996 Apr-Jun;2(2):141-4. [Medline].
• Jackson LA, Spach DH, Kippen DA, et al. Seroprevalence to Bartonella quintana among patients at a community clinic in downtown Seattle. J Infect Dis. 1996 Apr;173(4):1023-6. [Medline].
• La VD, Tran-Hung L, Aboudharam G. Bartonella quintana in domestic cat. Emerg Infect Dis. Aug 2005;11(8):1287-9.
• LaScola B, Raoult D. Culture of Bartonella quintana and Bartonella henselae from human samples: a 5-year experience (1993 to 1998). J Clin Microbiol. 1999 Jun;37(6):1899-905. [Medline].
• Maurin M, Birtles R, Raoult D. Current knowledge of Bartonella species. Eur J Clin Microbiol Infect Dis. Jul 1997;16(7):487-506. [Medline].
• Maurin M, Raoult D. Bartonella (Rochalimaea) quintana infections. Clin Microbiol Rev. Jul 1996;9(3):273-92. [Medline].
• Myers WF, Grossman DM, Wisseman CL Jr. Antibiotic susceptibility patterns in Rochalimaeaquintana, the agent of trench fever. Antimicrob Agents Chemother. 1984;25:690-3. [Medline].
• Raoult D, Birtles RJ, Montoya M, et al. Survey of three bacterial louse-associated diseases among rural Andean communities in Peru: prevalence of epidemic typhus, trench fever, and relapsing fever. Clin Infect Dis. Aug 1999;29(2):434-6. [Medline].
• Raoult D, Roux V. The body louse as a vector of reemerging human diseases. Clin Infect Dis. 1999 Oct;29(4):888-911. [Medline].
• Roux V, Raoult D. Inter- and intraspecies identification of Bartonella (Rochalimaea) species [see comments]. J Clin Microbiol. Jun 1995;33(6):1573-9. [Medline].
• Rydkina EB, Roux V, Gagua EM, et al. Bartonella quintana in body lice collected from homeless persons in Russia [letter]. Emerg Infect Dis. Jan-Feb 1999;5(1):176-8. [Medline].
• Spach DH, Koehler JE. Bartonella-associated infections. Infect Dis Clin North Am. Mar 1998;12(1):137-55. [Medline].
• Stein A, Raoult D. Return of trench fever [letter]. Lancet. Feb 18 1995;345(8947):450-1. [Medline].
• Tappero JW, Koehler JE. Rochalimaea infections. Ann Intern Med. 1993;119:535-6. [Medline].
• Tompkins LS. Bartonella species infections, including cat-scratch disease, trench fever, and bacillary angiomatosis--what molecular techniques have revealed. West J Med. Jan 1996;164(1):39-41. [Medline].
• Varela G, Vinson JW, Molina-Pasquel C. Trench fever. II. Propagation of Rickettsiaquintana on cell-free medium from the blood oftwo patients. Am J Trop Med Hyg. 1969;18:708-12. [Medline].
• Vinson JW, Varela G, Molina-Pasquel C. Trench fever. 3. Induction of clinical disease involunteers inoculated with Rickettsia quintanapropagated on blood agar. Am J Trop Med Hyg. 1969;18:713-22. [Medline].
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Article Last Updated: Jun 26, 2006