Bartonellosis is an infectious disease produced by bacteria of the genus Bartonella. Bartonella species cause diseases such as Carrión´s disease, trench fever, cat-scratch disease, bacillary angiomatosis, peliosis hepatis, chronic bacteremia, endocarditis, chronic lymphadenopathy, and neurological disorders.
- 1 Presentation
- 2 Microbiology
- 3 Pathophysiology
- 4 Diagnosis
- 5 Treatment
- 6 Epidemiology
- 7 History of discovery
- 8 References
- 9 External links
Patients can develop two clinical phases: an acute septic phase and a chronic eruptive phase associated with skin lesions. In the acute phase (also known as Oroya fever or fiebre de la Oroya), B. bacilliformis infection is a sudden, potentially life-threatening infection associated with high fever and decreased levels of circulating red blood cells (i.e., hemolytic anemia)and transient immunosuppression. B. bacilliformis is considered the most deadly species to date, with a death rate of up to 90% during the acute phase, which typically lasts two to four weeks. Peripheral blood smears show anisomacrocytosis with many bacilli adherent to red blood cells. Thrombocytopenia is also seen and can be very severe. Neurologic manifestations (neurobartonellosis) are altered mental status, agitation, or even coma, ataxia, spinal meningitis, or paralysis. It is seen in 20% of patients with acute infection, in which the prognosis is very guarded with an about 50% mortality. The most feared complication is overwhelming infection mainly by Enterobacteriaceae, particularly Salmonella (both S. typhi and S. non-typhi, as well as reactivation of toxoplasmosis and other opportunistic infections .
The chronic manifestation consists of a benign skin eruption with raised, reddish-purple nodules (angiomatous tumours). The bacterium can be seen microscopically, if a skin biopsy is silver stained (the Warthin–Starry method).
Cat-scratch disease is due to an infection by B. henselae and manifests as gradual regional lymph nodes enlargement (axilla, groin, neck) which may last 2–3 months or longer and a distal scratch and/or red-brown skin papule (not always seen at the time of the disease). The enlarged lymph node is painful and tender. The lymph nodes may suppurate, some patients may remain afebrile or asymptomatic. Other presentations include fever (particularly in children), Parinaud's oculoglandular syndrome, encephalopathy, and neuroretinitis.
B. henselae can be associated with bacteremia, bacillary angiomatosis, and peliosis hepatis in HIV patients, and bacteremia and endocarditis in immunocompetent and immunocompromised patients. Symptoms may include fatigue, headaches, fever, memory loss, disorientation, insomnia, and loss of coordination. The bacteria block the normal immune response by suppressing the NF-κB apoptosis pathway. Disease progression may be accelerated if the host is subsequently infected by an immune-suppressing virus such as Epstein Barr virus.
B. henselae and B. quintana can cause bacillary angiomatosis, a vascular proliferative disease involving mainly the skin, and other organs. The disease was first described in human immunodificiency virus (HIV) patients and organ transplant recipients. Severe, progressive and disseminated disease may occur in HIV patients. Differential diagnoses include Kaposi´s sarcoma, pyogenic granuloma, hemangioma, verruga Peruana, and subcutanous tumors. Lesions can affect bone marrow, liver, spleen, or lymph nodes.
B. henselae is the etiologic agent for peliosis hepatis, which is defined as a vascular proliferation of sinusoid hepatic capillaries resulting in blood-filled spaces in the liver in HIV patients and organ transplant recipients. Peliosis hepatis can be associated with peliosis of the spleen, as well as bacillary angiomatosis of the skin in HIV patients.
Trench fever, also known as five-day fever or quintan fever, is the initial manifestation of B. quintana infection. Clinical manifestations range from asymptomatic infection to severe illness. Classical presentations include a febrile illness of acute onset, headache, dizziness, and shin pain. Chronic infection manifestations include attacks of fever and aching in some cases and persistent bacteremia in soldiers and homeless people.
|Bartonella bacilliformis||human||Carrion´s disease/verruga Peruana|
|Bartonella quintana||human||Trench fever, bacteremia, bacillary angiomatosis, endocarditis|
|Bartonella henselae||cats||Cat-scratch disease, bacillary angiomatosis, bacteremia, endocarditis, encephalitis, meningitis|
|Bartonella vinsoni||dogs||Endocarditis], bacteremia|
|Bartonella rochalimae||human||Carrion´s disease-like syndrome|
In mammals, each Bartonella species is highly adapted to its reservoir host as the result of intracellular parasitism and can persist in the bloodstream of the host. Intraerythrocytic parasitism is only observed in the acute phase of Carrión´s disease. Bartonella species also have a tropism for endothelial cells, observed in the chronic phase of Carrión´s disease (also known as verruga Peruana) and bacillary angiomatosis. Pathological response can vary with the immune status of the host. Infection with B. henselae can result in a focal suppurative reaction (CSD in immunocompetent patients), a multifocal angioproliferative response (bacillary angiomatosis in immunocompromised patients), endocarditis, or meningitis.
There are several methods used for diagnosing Bartonella infection including microscopy, serology, and PCR. Microscopy of blood smears is used to diagnose Carrión’s disease (B. bacilliformis), however for other Bartonella species, microscopy and silver staining are insensitive, not highly specific, and cannot differentiate species. The CDC does not recommend lymph node aspiration for diagnostic purposes.
Serology and protein-based methods
IFA (immunofluorescence antibody assay) testing for the presence of antibodies in serum is used to diagnose B. henselae infection at the acute onset of Cat Scratch Disease symptoms, followed by PCR to confirm infecting species. IFA can generally be used to confirm a diagnosis of Bartonella infection, but is limited by antibody cross-reactivity with other bacteria species  which can cause a false positive, and antigen variability which can result in false negatives.
Bartonella spp. often evade an immune response, thus antibodies may not be detected even concurrent with an infection, resulting in an IFA false negative rate of up to 83% in chronically infected patients when other test results (e.g. organism isolation or PCR) are positive. IFA sensitivity may range from 14-100%, causing discrepancies between PCR and serology test results. Positive IFA results do not distinguish between current infection and prior exposure.
ELISA (enzyme-linked immunosorbent assay) is another method that has been used to detect Bartonella, but it has a low sensitivity (17-35%). Western blot for protein detection of Bartonella-associated proteins has also been reported, but this method does not show clear immunoreactive profiles.
The CDC states that PCR testing from a single blood draw is not sufficiently sensitive for B. henselae testing, and can result in high false negative rates  due to a small sample volume and levels below the limit of molecular detection.
Bartonella spp. are fastidious, slow-growing bacteria that are difficult to grow using traditional solid agar plate culture methods due to complex nutritional requirements and potentially a low number of circulating bacteria. This conventional method of culturing Bartonella spp. from blood inoculates plated directly onto solid agar plates requires an extended incubation period of 21 days due to the slow growth rate.
Bartonella growth rates improve when cultured in an enrichment inoculation step in a liquid insect-based medium  such as Bartonella α-Proteobacteria Growth Medium (BAPGM)  or Schneider’s Drosophila-based insect powder medium. Several studies have optimized the growing conditions of Bartonella spp. cultures in these liquid media, with no change in bacterial protein expressions or host interactions in vitro. Insect-based liquid media supports the growth and co-culturing of at least seven Bartonella species, reduces bacterial culturing time and facilitates PCR detection and isolation of Bartonella spp. from animal and patient samples. Research shows that DNA may be detected following direct extraction from blood samples and become negative following enrichment culture, thus PCR is recommended after direct sample extraction and also following incubation in enrichment culture. Several studies have successfully optimized sensitivity and specificity by using PCR amplification (pre-enrichment PCR) and enrichment culturing of blood draw samples, followed by PCR (post-enrichment PCR) and DNA sequence identification.
|Cat-scratch disease||Azithromycin + Rifampin||Unknown|
|Retinitis||Doxycycline + rifampin||unknown|
|Trench fever or chronic bacteremia by B. quintana||Doxycycline + gentamicin||unknown|
|Bacillary angiomatosis||Erythromycin or doxycycline||Erythromycin|
|Peliosis hepatis||Erythromycin or doxycycline||Erythromycin|
|Endocarditis||Doxycycline + gentamicin + rifampin or ceftriaxone + gentamicin|
|Carrión´s disease (acute phase)||Ciprofloxacin or chloramphenicol||Chloramphenicol + beta-lactam|
|Carrión´s disease (chronic phase)||Rifampin or macrolides||Rifampin or macrolides|
Carrión's disease, or Oroya fever, or Peruvian wart is a rare infectious disease found only in Peru, Ecuador, and Colombia. It is endemic in some areas of Peru, is caused by infection with the bacterium Bartonella bacilliformis, and transmitted by sandflies of genus Lutzomyia.
Cat scratch disease occurs worldwide. Cats are the main reservoir of Bartonella henselae, and the bacterium is transmitted to cats by the cat flea Ctenocephalides felis. Infection in cats is very common with a prevalence estimated between 40-60%, younger cats being more commonly infective. Cats usually become immune to the infection, while dogs may be very symptomatic. Humans may also acquire it through flea or tick bites from infected dogs, cats, coyotes, and foxes.
Trench fever, produced by Bartonella quintana infection, is transmitted by the human body louse Pediculus humanus corporis. Humans are the only known reservoir. Thorough washing of clothing may help to interrupt the transmission of infection.
A possible role for ticks in transmission of Bartonella species remains to be elucidated; in November 2011, Bartonella rochalimae, B. quintana, and B. elizabethae DNA was first reported in Rhipicephalus sanguineus and Dermacentor nitens ticks in Peru.
History of discovery
The disease was named after medical student Daniel Alcides Carrión from Cerro de Pasco, Peru. Carrión described the disease after being inoculated at his request with the pus of a skin lesion from patient Carmen Paredes in 1885 by Doctor Evaristo M. Chávez, a close friend and coworker in Dos de Mayo National Hospital. Carrión developed the disease three weeks after the inoculation and kept a meticulous record of clinical symptoms and signs until the disease rendered him incapable of the task and he died at age 28 several weeks later—October 5, 1885. Carrión proved that Oroya fever and verruga peruana were two stages of the same disease, and not two different diseases as was thought at the time. His work did not result in a cure immediately, but his research started the process. Peru has named October 5 as "Peruvian Medicine Day" in his honor.
Peruvian microbiologist Alberto Barton discovered the causative bacterium in 1905, but his results were not published until 1909. Barton originally identified them as "endoglobular" structures, bacteria living inside red blood cells. Until 1993, the genus Bartonella, within the family Bartonellaceae, contained only one species; 23 are now identified.
In 1988, English et al.  isolated and cultured a bacterium that was named Afipia felis in 1992 after the team at the Armed Forces Institute of Pathology that discovered it. This agent was considered the cause of cat-scratch Disease (CSD) but further studies failed to support this conclusion. Serologic studies associated CSD with Bartonella henselae, reported in 1992. In 1993, Dolan  isolated Rochalimae henselae (now called Bartonella henselae) from lymph nodes of patients with CSD.
Bartonella spp. are commonly treated with antibiotics including azithromycin, based on a single small randomized clinical trial. Treatment may take up to one year to completely eliminate the disease. CSD often resolves spontaneously without treatment.
Detailed descriptions of the disease were reported in soldiers during the First World War. It is also known as five-day fever, quintan fever, Wolhinie fever, and urban trench fever, because it occurs in homeless people and alcoholics .
- Maguiña C, Gotuzzo E (March 2000). "Bartonellosis. New and old". Infect. Dis. Clin. North Am. 14 (1): 1–22, vii. doi:10.1016/S0891-5520(05)70215-4. PMID 10738670.
- Maurin M, Birtles R, Raoult D (July 1997). "Current knowledge of Bartonella species". Eur. J. Clin. Microbiol. Infect. Dis. 16 (7): 487–506. doi:10.1007/BF01708232. PMID 9272384.
- Maguiña Vargas, Ciro (2010). Bartonellosis o enfermedad de Carrión: Nuevos aspectos de una vieja enfermedad. Lima, Peru: UNMSM, Fondo Editorial. ISBN 978-9972-50-034-3.
- Bass JW, Vincent JM, Person DA (February 1997). "The expanding spectrum of Bartonella infections: II. Cat-scratch disease". Pediatr. Infect. Dis. J. 16 (2): 163–79. doi:10.1097/00006454-199702000-00002. PMID 9041596.
- Breitschwerdt, EB. Bartonella sp. Bacteremia in Patients with Neurological and Neurocognitive Dysfunction. JOURNAL OF CLINICAL MICROBIOLOGY. Sept. 2008. 46(9): 2856–2861
- Anderson BE, Neuman MA (April 1997). "Bartonella spp. as emerging human pathogens". Clin. Microbiol. Rev. 10 (2): 203–19. doi:10.1128/CMR.10.2.203. PMC 172916. PMID 9105751.
- Faherty, CS. Staying alive: bacterial inhibition of apoptosis during infection Archived July 8, 2011, at the Wayback Machine. Trends in Microbiology (16:4). 175.
- citation needed
- Kemper CA, Lombard CM, Deresinski SC, Tompkins LS (August 1990). "Visceral bacillary epithelioid angiomatosis: possible manifestations of disseminated cat scratch disease in the immunocompromised host: a report of two cases". Am. J. Med. 89 (2): 216–22. doi:10.1016/0002-9343(90)90301-S. PMID 2382668.
- Stoler MH, Bonfiglio TA, Steigbigel RT, Pereira M (November 1983). "An atypical subcutaneous infection associated with acquired immune deficiency syndrome". Am. J. Clin. Pathol. 80 (5): 714–8. doi:10.1093/ajcp/80.5.714. PMID 6637883.
- Perkocha LA, Geaghan SM, Yen TS, et al. (December 1990). "Clinical and pathological features of bacillary peliosis hepatis in association with human immunodeficiency virus infection". N. Engl. J. Med. 323 (23): 1581–6. doi:10.1056/NEJM199012063232302. PMID 2233946.
- Brouqui P, Lascola B, Roux V, Raoult D (January 1999). "Chronic Bartonella quintana bacteremia in homeless patients". N. Engl. J. Med. 340 (3): 184–9. doi:10.1056/NEJM199901213400303. PMID 9895398.
- "Clinicians | Bartonella | CDC". www.cdc.gov. Retrieved 2016-01-19.
- Versalovic, James (2011). Manual of Clinical Microbiology, 10th Edition. ASM Press. pp. 786–798. ISBN 978-1555814632.
- Sander, A (1998). "Seroprevalence of antibodies to Bartonella henselae in patients with cat scratch disease and in healthy controls: evaluation and comparison of two commercial serological tests". Clin Diagn Lab Immunol. 5 (4): 486–90. PMC 95604. PMID 9665953.
- Vermeulen, M (2010). "Evaluation of sensitivity, specificity and cross-reactivity in Bartonella henselae serology". J Med Microbiol. 59 (Pt 6): 743–5. doi:10.1099/jmm.0.015248-0. PMID 20223899.
- Duncan, A (2007). "A combined approach for the enhanced detection and isolation of Bartonella species in dog blood samples: pre-enrichment liquid culture followed by PCR and subculture onto agar plates". J Microbiol Methods. 69 (2): 273–81. doi:10.1016/j.mimet.2007.01.010. PMID 17346836.
- Wolf, L (2014). "In Pursuit of a Stealth Pathogen: Laboratory Diagnosis of Bartonellosis". Clinical Microbiology Newsletter. 36 (5): 33–39. doi:10.1016/j.clinmicnews.2014.02.001.
- Bai, Y (2010). "Enrichment culture and molecular identification of diverse Bartonella species in stray dogs". Vet Microbiol. 146 (3–4): 314–9. doi:10.1016/j.vetmic.2010.05.017. PMID 20570065.
- Clarridge, J (1995). "Strategy to detect and identify Bartonella species in routine clinical laboratory yields Bartonella henselae from human immunodeficiency virus-positive patient and unique Bartonella strain from his cat". J Clin Microbiol. 33 (8): 2107–13. PMC 228344. PMID 7559957.
- Riess, T (2008). "Analysis of a novel insect cell culture medium-based growth medium for Bartonella species". Appl Environ Microbiol. 74 (16): 5224–7. doi:10.1128/AEM.00621-08. PMC 2519262. PMID 18567689.
- Lynch, T (2011). "Combining culture techniques for Bartonella: the best of both worlds". J Clin Microbiol. 49 (4): 1363–8. doi:10.1128/JCM.02403-10. PMC 3122786. PMID 21289156.
- Bai, Y (2012). "Bartonella vinsonii subsp. arupensis in humans, Thailand". Emerg Infect Dis. 18 (6): 989–91. doi:10.3201/eid1806.111750. PMC 3358162. PMID 22607728.
- Pultorak, E (2013). "Serial testing from a 3-day collection period by use of the Bartonella Alphaproteobacteria growth medium platform may enhance the sensitivity of Bartonella species detection in bacteremic human patients". J Clin Microbiol. 51 (6): 1673–7. doi:10.1128/JCM.00123-13. PMC 3716093. PMID 23486720.
- Rolain JM, Brouqui P, Koehler JE, Maguina C, Dolan MJ, Raoult D (June 2004). "Recommendations for treatment of human infections caused by Bartonella species". Antimicrob. Agents Chemother. 48 (6): 1921–33. doi:10.1128/AAC.48.6.1921-1933.2004. PMC 415619. PMID 15155180.
- Blanco JR, Raoult D (May 2005). "[Diseases produced by Bartonella]". Enferm. Infecc. Microbiol. Clin. (in Spanish). 23 (5): 313–9, quiz 320. PMID 15899181.
- Bass JW, Freitas BC, Freitas AD, et al. (June 1998). "Prospective randomized double blind placebo-controlled evaluation of azithromycin for treatment of cat-scratch disease". Pediatr. Infect. Dis. J. 17 (6): 447–52. doi:10.1097/00006454-199806000-00002. PMID 9655532.
- Maguina C, Garcia PJ, Gotuzzo E, Cordero L, Spach DH (September 2001). "Bartonellosis (Carrión's disease) in the modern era". Clin. Infect. Dis. 33 (6): 772–9. doi:10.1086/322614. PMID 11512081.
- Maco V, Maguiña C, Tirado A, Maco V, Vidal JE (2004). "Carrion's disease (Bartonellosis bacilliformis) confirmed by histopathology in the High Forest of Peru". Rev. Inst. Med. Trop. Sao Paulo. 46 (3): 171–4. doi:10.1590/S0036-46652004000300010. PMID 15286824.
- Chomel BB, Kasten RW, Floyd-Hawkins K, et al. (August 1996). "Experimental transmission of Bartonella henselae by the cat flea". J. Clin. Microbiol. 34 (8): 1952–6. PMC 229161. PMID 8818889.
- Maurin M, Raoult D (July 1996). "Bartonella (Rochalimaea) quintana infections". Clin. Microbiol. Rev. 9 (3): 273–92. doi:10.1128/CMR.9.3.273. PMC 172893. PMID 8809460.
- Billeter Sarah A.; Cáceres Abraham G.; Gonzales-Hidalgo James; Luna-Caypo Deysi; Kosoy Michael Y. (2011). "Molecular Detection of Bartonella Species in Ticks From Peru". Journal of Medical Entomology. 48 (6): 1257–1260. doi:10.1603/me10240.
- Zeaiter Z, Liang Z, Raoult D (2002). "Genetic classification and differentiation of Bartonella species based on comparison of partial ftsZ gene sequences". J. Clin. Microbiol. 40 (10): 3641–7. doi:10.1128/JCM.40.10.3641-3647.2002. PMC 130884. PMID 12354859.
- English CK, Wear DJ, Margileth AM, Lissner CR, Walsh GP (March 1988). "Cat-scratch disease. Isolation and culture of the bacterial agent". JAMA. 259 (9): 1347–52. doi:10.1001/jama.259.9.1347. PMID 3339840.
- Dolan MJ, Wong MT, Regnery RL, et al. (March 1993). "Syndrome of Rochalimaea henselae adenitis suggesting cat scratch disease". Ann. Intern. Med. 118 (5): 331–6. doi:10.7326/0003-4819-118-5-199303010-00002. PMID 8430978.
- Resto-Ruiz S, Burgess A, Anderson BE (June 2003). "The role of the host immune response in pathogenesis of Bartonella henselae". DNA Cell Biol. 22 (6): 431–40. doi:10.1089/104454903767650694. PMID 12906736.
- Stein A, Raoult D (February 1995). "Return of trench fever". Lancet. 345 (8947): 450–1. doi:10.1016/S0140-6736(95)90430-1. PMID 7853966.