Facts about Bartonella quintana infection (‘trench fever’)

factsheet

Disclaimer: The information contained in this factsheet is intended for the purpose of general information and should not substitute individual expert advice and judgement of healthcare professionals.

Introduction 

Bartonella quintana infection (historically called ‘trench fever’) is a vector-borne disease primarily transmitted by the human body louse Pediculus humanus humanus. The infection is associated with a wide variety of clinical conditions, including chronic bacteraemia, endocarditis, lymphadenopathy and bacillary angiomatosis. Since the 1990s, it has been recognised as a reemerging pathogen among impoverished and homeless populations — so-called ‘urban trench fever’ — living in unsanitary conditions and crowded areas predisposing them to infestation with ectoparasites that may transmit the infection. Primary prevention of trench fever relies on measures for avoiding infestation with body lice.

The pathogen  

  • B. quintana is slow-growing Gram-negative bacterium with short rods morphology (0.3 to 0.5 mm wide and 1.0 to 1.7 mm long).
  • B. quintana has a circular chromosome (≈1.6 Mb) recognised as a genomic derivative of Bartonella henselae, the causative agent of cat scratch disease [1].

Clinical features and sequelae 

  • The incubation period is usually between 15 and 25 days but has been reported as shorter, up to six days, under experimental conditions [2].
  • Clinical manifestations of B. quintana infection include the classical recurrent fever ‘trench fever’, chronic bacteraemia, endocarditis and, among immunocompromised individuals, bacillary angiomatosis. Lymphadenopathy and ocular complications are occasionally reported.
    • Trench fever or quintana fever (5-day fever) is a recurrent fever among non-immunocompromised individuals. Fever episodes lasting for one to five days are associated with nonspecific and varying symptoms such as severe headache, tenderness or pain in the shin, weakness, anorexia or abdominal pain. Splenomegaly is common. The number of periodic fever episodes varies (from one to five in general) and are separated with asymptomatic periods of four to six days. Episodes usually decrease in severity over time [2]. Although it causes prolonged disability, the mortality of trench fever is low.
    • Chronic bacteraemia is possible due the ability of B. quintana to cause intraerythrocytic paratism that can be asymptomatic [3]. This has been demonstrated in both immunocompromised and immunocompetent patients.
    • B. quintana infection is a significant cause of blood culture-negative endocarditis. Fever is frequently reported. Valvular vegetations are often visible on echocardiography. Laboratory confirmation assays can be performed on cardiac valve if surgery is required.

 

Bacillary angiomatosis is a proliferative vascular disease due to both B. quintana and B. henselae. The disease is characterised by angioproliferative lesions of skin (sarcoma-like skin lesions) or various organs (spleen, liver, bone marrow and lymph nodes) [4]. Bacillary angiomatosis due to B. quintana was mainly reported among immunodeficiency virus-infected persons in the 1990s, but can affect other immunocompromised individuals.

 

  • Differential diagnoses vary according to the clinical presentation, and include:
    • Trench fever: louse-borne and tick-borne relapsing fever, infection due to B. henselae (cat scratch disease), typhus, malaria, typhoid and non-typhoid salmonellosis.
    • Endocarditis: HACEK group infections, fastidious growing streptococci endocarditis, legionellosis and Q fever.
    • Bacillary angiomatosis: Kaposi sarcoma, pyogenic granuloma, or Peruvian wart (verruga peruana) due to Bartonella bacilliformis.
    • Lymphadenopathy: infectious (fungal infection, tularaemia, tuberculosis, plague, lymphogranuloma venereum (LGV), AIDS, and syphilis) and non-infectious causes (lymphoma, leukemia and other neoplasms).

 

Epidemiology 

  • Historically, trench fever was described in relation to outbreaks among soldiers during the first and second world wars. Since then, few cases have been documented, mainly in Europe and Russia. The disease is considered to have a worldwide distribution based on serological evidence and molecular identification (Africa and South-east Asia notably) [4,5].
  • During the 1990s, B. quintana infections and outbreaks were reported among the homeless in USA and Europe (France) leading to the infection being recognised as a re-emerging disease among deprived populations. The main risk factors for infection are impoverished, overcrowded and unhygienic conditions, chronic alcoholism, cat-contact, and body louse infestation. The disease is therefore primarily observed among homeless people.
  • Small case series of B. quintana infections were reported among immunocompetent patients without body louse infestation: a family cluster with pigeon mites (Dermanyssus sp.) as the presumed vector in Czech Republic (2007) and three pediatric cases of lymphadenopathy in Italy (2014) [6,7].
  • Humans are considered the main host for this organism but several publications have reported isolation or molecular identification of the bacteria in mammals (macaques, cats and dogs) [8].

 

Transmission 

  • B. quintana is transmitted from human to human by the body louse Pediculus humanus humanus. However head lice, Pediculus humanus capitis, have been found to be infected, but their role as a vector has not been established.
  • B. quintana DNA has been identified from severalarthropods (ticks, bed bugs, cat- and rodent- fleas) but the epidemiological role of these arthropods in transmission of the pathogen is not established yet [4,9-13].
  • When feeding on an infected human, the body louse ingests B. quintana which multiplies in the intestinal tract of the body louse. Body louse infection is lifelong. B. quintana is excreted in body louse faeces.
  • Infected dried body louse faeces can remain infectious for 12 months and new cases can arise for some time even after elimination of the louse population [8,14].
  • Human infection probably results from inoculation of B. quintana from contaminated louse faeces when scratching and itching. The transmission does not invoke the death of the louse, therefore an individual louse can spread the disease to several persons.
  • On average a mature body louse lives for 20–30 days. 

 

Diagnostics 

  • The laboratory diagnostic of choice is isolation in culture from blood or tissues on specific media under specific conditions.
  • Due the low-growing characteristic of B. quintana, diagnosis is often based on supportive diagnostic tests such as serology or polymerase chain reaction (PCR) based genomic assays.
  • Regarding serological test, indirect immunofluorescence assay is the reference method. However cross reactions are possible, notably with other Bartonella species. High levels of antibodies are usually detected among immunocompetent patients with endocarditis related to B. quintana. Serologic testing cannot stand alone as a means to confirm Bartonella infection and should be interpreted in the context of the clinical presentation, immunological status of the patient and results of others supporting laboratory test.
  • Immunohistochemical tests are supportive of the diagnosis of bacillary angiomatosis or identification with biopsies (cardiac valve, lymph node, skin or other tissue).
  • PCR–based genomic assays on blood and tissues can distinguish Bartonella species in targeting specific genes.

 

Case management and treatment [2,15,16]  

  • Information on efficacy of treatment is limited due to the small number of studies available and so choice of treatment relies on expert recommendations. Note that doxycycline should not be used in children as tooth discoloration is a concern.
  • Antibiotic treatment protocols are different according to the disease presentation:
    • Trench fever and chronic bacteraemia: doxycycline 200 mg orally daily for 28 days combined with gentamicin 3 mg/kg/day intravenous for 14 days.
    • Endocarditis: doxycycline 100 mg orally twice daily for six weeks combined with gentamicin 3 mg/kg/day intravenous for 14 days.
    • Bacillary angiomatosis: erythromycin 500 mg orally four times daily for three months (first line therapy) or doxycycline 100 mg orally twice daily for three months (alternative therapy); in refractory cases, gentamicin 3 mg/kg/day IV for 14 days can be added. Ceftriaxone and fluoroquinolones may also be considered as an alternative therapy.

 

Infection control, personal protection and prevention [14]

  • Primary prevention of B. quintana relies on measures to avoid infestation with body lice.
  • Body louse infestations are linked to low socioeconomic status, over-crowding and poor personal hygiene.
  • Body lice are transmitted primarily by direct contact with an infested person; transmission of the body lice also occurs through fomites, clothes or bedding. Lice multiply rapidly and a population can increase by 11% per day.
  • Body lice are highly susceptible to cold and desiccation. They are found on clothing close to the human skin. Discarding infested clothes is an effective way to control the infestation. If this is not possible, clothes should be washed at a temperature above 60ºC. Oral ivermectin for body delousing has been proposed for populations with low compliancy but does not protect from lice reinfestation.
  • In outbreak situations, dusting powder with an appropriate insecticide has been applied to obtain a rapid decrease of infested persons with some lasting benefits.
  • Although there are no reports of transmission, a risk of B.quintana infection by substances of human origin (SoHO) cannot be excluded because of possible donations by asymptomatic donors with bacteraemia [17]. In addition, a case of possible transfusion transmission of the closely related B. henselae has been reported [18,19]. Due to possible transmissibility through SoHO, infected donors should be deferred for at least two weeks after signs and symptoms have resolved and a course of effective treatment has been completed. Donation of organs, cells and tissues from deceased donors with a trench fever is not recommended.

 

List of references 

1.         Alsmark CM, Frank AC, Karlberg EO, Legault BA, Ardell DH, Canback B, et al. The louse-borne human pathogen Bartonella quintana is a genomic derivative of the zoonotic agent Bartonella henselae. Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9716-21.
2.         Foucault C, Brouqui P, Raoult D. Bartonella quintana characteristics and clinical management. Emerg Infect Dis. 2006 Feb;12(2):217-23.
3.         Foucault C, Barrau K, Brouqui P, Raoult D. Bartonella quintana Bacteremia among Homeless People. Clin Infect Dis. 2002 Sep 15;35(6):684-9.
4.         Maurin M, Raoult D. Bartonella (Rochalimaea) quintana infections. Clin Microbiol Rev. 1996 Jul;9(3):273-92.
5.         Sangare AK, Boutellis A, Drali R, Socolovschi C, Barker SC, Diatta G, et al. Detection of Bartonella quintana in African body and head lice. Am J Trop Med Hyg. 2014 Aug;91(2):294-301.
6.         Magnolato A, Pederiva F, Spagnut G, Maschio M, Ventura A, Taddio A. Three cases of Bartonella quintana infection in children. Pediatr Infect Dis J. 2015 May;34(5):540-2.
7.         Melter O, Arvand M, Votypka J, Hulinska D. Bartonella quintana transmission from mite to family with high socioeconomic status. Emerg Infect Dis. 2012 Jan;18(1):163-5.
8.         Chomel BB, Boulouis HJ, Breitschwerdt EB, Kasten RW, Vayssier-Taussat M, Birtles RJ, et al. Ecological fitness and strategies of adaptation of Bartonella species to their hosts and vectors. Vet Res. 2009 Mar-Apr;40(2):29.
9.         Billeter SA, Caceres AG, Gonzales-Hidalgo J, Luna-Caypo D, Kosoy MY. Molecular detection of Bartonella species in ticks from Peru. J Med Entomol. 2011 Nov;48(6):1257-60.
10.        Morozova OV, Chernousova N, Morozov IV. [Detection of the Bartonella DNA by the method of nested PCR in patients after tick bites in Novosibirsk region]. Mol Gen Mikrobiol Virusol. 2005 (4):14-7.
11.        Marie JL, Fournier PE, Rolain JM, Briolant S, Davoust B, Raoult D. Molecular detection of Bartonella quintana, B. Elizabethae, B. Koehlerae, B. Doshiae, B. Taylorii, and Rickettsia felis in rodent fleas collected in Kabul, Afghanistan. Am J Trop Med Hyg. 2006 Mar;74(3):436-9.
12.        Leulmi H, Bitam I, Berenger JM, Lepidi H, Rolain JM, Almeras L, et al. Competence of Cimex lectularius Bed Bugs for the Transmission of Bartonella quintana, the Agent of Trench Fever. PLoS Negl Trop Dis. 2015 May;9(5):e0003789.
13.        Kernif T, Leulmi H, Socolovschi C, Berenger JM, Lepidi H, Bitam I, et al. Acquisition and excretion of Bartonella quintana by the cat flea, Ctenocephalides felis felis. Mol Ecol. 2014 Mar;23(5):1204-12.
14.        Raoult D, Roux V. The body louse as a vector of reemerging human diseases. Clin Infect Dis. 1999 Oct;29(4):888-911.
15.        Rolain JM, Brouqui P, Koehler JE, Maguina C, Dolan MJ, Raoult D. Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother. 2004 Jun;48(6):1921-33.
16.        Prutsky G, Domecq JP, Mori L, Bebko S, Matzumura M, Sabouni A, et al. Treatment outcomes of human bartonellosis: a systematic review and meta-analysis. Int J Infect Dis. 2013 Oct;17(10):e811-9.
17.        Brouqui P, Lascola B, Roux V, Raoult D. Chronic Bartonella quintana bacteremia in homeless patients. N Engl J Med. 1999 Jan 21;340(3):184-9.
18.        Magalhaes RF, Pitassi LH, Salvadego M, de Moraes AM, Barjas-Castro ML, Velho PE. Bartonella henselae survives after the storage period of red blood cell units: is it transmissible by transfusion? Transfus Med. 2008 Oct;18(5):287-91.
19.        Velho PE. Blood transfusion as an alternative bartonellosis transmission in a pediatric liver transplant. Transpl Infect Dis. 2009 Oct;11(5):474.