Bartonellosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Bartonellosis is an infectious disease produced by bacteria of the genus Bartonella.^[1] Bartonella cause diseases such as Carrión´s disease, trench fever, cat-scratch disease, severe obesity, bacillary angiomatosis, peliosis hepatis, chronic bacteremia, endocarditis, chronic lymphadenopathy, and neurological disorders.^[2]

Bartonellosis is caused by the bacteria belonging to the Bartonella genus containing 23 identified species, all of them within family Bartonellaceae.

Carrión’s disease, or Oroya fever, or Peruvian Wart is a rare infectious disease found only in Peru, Ecuador, and Colombia.^[3] It is endemic in some areas of Peru,^[4] and is caused by infection with the bacterium Bartonella bacilliformis and transmitted by sandflies of genus Lutzomyia.

Cat scratch disease is a worldwide disease. Cats are the main reservoir of Bartonella henselae (etiologic agent), and the bacterium is transmitted to cats by the cat flea Ctenocephalides felis.^[5]

Trench fever is produced by Bartonella quintana infection, and the bacterium is transmitted by the human body louse Pediculus humanus corporis. Humans are the only known reservoir.^[6]

In November 2011, Bartonella rochalimae, B. quintana, and B. elizabethae DNA was first reported in Rhipicephalus sanguineus and Dermacentor nitens ticks in Peru; a possible role for ticks in transmission of Bartonella species remains to be elucidated.^[7]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

In 1988, English et al. ^[1] isolated and cultured a bacterium that was named Afipia felis in 1992. This agent was considered the etiologic agent 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 ^[2] isolated Rochalimae henselae (now called Bartonella henselae) from the lymph nodes of patients with CSD. Also, Bartonella henselae was associated bacteremia, bacillary angiomatosis, and peliosis hepatis in HIV patients, and bacteremia and endocarditis in immunocompetent and immunocompromised patients.^[3]

Detailed descriptions of the disease were reported in soldiers during the First World War. It is also known as five-day fever, quintan fever, and Wolhinie fever. This disease is also known as “urban trench fever” because it is described in homeless and alcoholic people.^[4]

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 by Doctor Evaristo M. Chávez, a close friend and coworker in Dos de Mayo National Hospital. Carrión kept a meticulous clinical history until the disease rendered him incapable of the task. Carrión proved that “Oroya fever” and “Verruga Peruana” were two stages of the same disease, not two different diseases as was thought at the time.

Carrión was inoculated with the pus of the purple lesion from a patient (Carmen Paredes) in 1885. He developed the disease three weeks after the inoculation and died several weeks later. Bartonella bacilliformis is considered the most deadly bartonella to date, with a death rate of up to 90% during the acute phase. His sacrifice demonstrated the connection between the two phases of the disease. Subsequently, 23 subspecies of bartonella were discovered. His work did not result in a cure immediately, but his research started the process. Peru named 5 October as Peruvian Medicine Day in his honor.

Peruvian microbiologist Alberto Barton discovered the causative bacterial agent of bartonellosis 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 Bartonella genus contained only one species; there are now 23 identified species, all of them within family Bartonellaceae.^[5]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Humans acquire it through flea or tick bites from infected dogs, cats, coyotes, foxes, and humans.^[1] Once bitten the victim develops a localized infection. The first sign of infection is a raised skin papule which resolves on its own. As the illness progresses, symptoms including fatigue, headaches, memory loss, disorientation, insomnia, and loss of coordination develop. The bacteria blocks the normal immune response by suppressing the NF-κB apoptosis pathway.^[2] Disease progression will be accelerated if the host is subsequently infected by an immunesuppressing virus such as Epstein Barr or XMRV and likewise, as the host’s infectious load increases the immune system will be more prone to infection due to the weakening response.

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 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 Bartonella henselae can result in a focal suppurative reaction (CSD in immunocompetent patients), a multifocal angioproliferative response (bacillary angiomatosis in immunocompromised patients), endocarditis or meningitis.

Some of the diseases can resolve spontaneously without treatment.^[3]

The clinical symptoms of Carrion’s disease are pleomorphic and some patients from endemic areas may be asymptomatic.

The two classical clinical presentations are the acute phase and the chronic phase, corresponding to the two different host cell types invaded by the bacterium (red blood cells and endothelial cells).

• Acute phase: (Carrion’s disease) the most common findings are fever (usually sustained, but with temperature no greater than 102°F (39°C)), malaise. This phase is characterized by severe hemolytic anemia and transient immunosuppression. The case fatality ratios of untreated patients exceeded 40% but reach around 90% when opportunistic infection with Salmonella species occurs. In a recent study the attack rate was 13.8% (123 cases) and the case-fatality rate was 0.7%.

• Chronic phase: (Verruga Peruana or Peruvian Wart) it is characterized by an eruptive phase, in which the patients develop a cutaneous rash produced by a proliferation of endothelial cells and is known as “Peruvian warts” or “verruga peruana”.

The most common findings are bleeding of verrugas, fever, malaise, arthralgias, anorexia, myalgias.

The condition is typically asymptomatic and is discovered following evaluation of abnormal liver function test. However, when severe it can manifest as jaundice, hepatomegaly, liver failure and haemoperitoneum.

The disease is classically a five-day fever of the relapsing type, rarely with a continuous course instead. Latent period is relatively long (about two weeks). The onset of symptoms is usually sudden with high fever, severe headache, pain on moving the eyeballs, soreness of the muscles of the legs and back, and frequently hyperaesthesia of the shins. The initial fever is usually followed in a few days by a single short rise but there may be many relapses between periods without fever. The most constant symptom is pain in the legs. Recovery takes a month or more. Lethal cases are rare, but in a few cases “the persistent fever might lead to heart failure”. After effects may include neurasthenia, cardiac disturbances and myalgia.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Faizan Sheraz, M.D. [2]

Bartonella (formerly known as Rochalimaea) is a genus of Gram-negative bacteria. Facultative intracellular parasites, Bartonella species can infect healthy people but are considered especially important as opportunistic pathogens.^[1] Bartonella are transmitted by insect vectors such as ticks, fleas, sand flies and mosquitoes. At least eight Bartonella species or subspecies are known to infect humans.^[2] In June 2007, a new species under the genus, called Bartonella rochalimae, was discovered.^[3] This is the sixth species known to infect humans, and the ninth species and subspecies, overall, known to infect humans.

Members of the genus Bartonella are alpha 2 subgroup Proteobacteria. The genus comprises:

Bartonella species have been infecting humans for thousands of years, as demonstrated by Bartonella quintana DNA in a 4000 year old tooth.^[4] The genus is named after Alberto Leonardo Barton Thompson, a Peruvian scientist born in Argentina.

Bartonella was found to be a tick borne pathogen in 1999.^[5]

In 2001 doctors treating Lyme disease first reported that their patients were co-infected with Bartonella.^[5] Multiple reports of this finding seem to indicate that Bartonella is not only a tick borne but a tick-transmitted pathogen;^[6] however, actual transmission via this route has not yet been proven.

The currently accepted model explaining the infection cycle holds that the transmitting vectors are blood-sucking arthropods and the reservoir hosts are mammals. Immediately after infection, the bacteria colonize a primary niche, the endothelial cells. Every five days, a part of the Bartonella in the endothelial cells are released in the blood stream where they infect erythrocytes. The bacteria then invade and replicate within a phagosomal membrane inside the erythrocytes. Inside the erythrocytes, bacteria multiply until they reach a critical population density. At this point, the Bartonella has simply to wait until it is taken with the erythrocytes by a blood-sucking arthropod.

Bartonella infections are remarkable in the wide range of symptoms an infection can produce: the time course (acute or chronic) as well as the underlying pathology are highly variable.^[7]

• Bartonella^[11]

• 1. Bartonella quintana

• 1.1 Acute or chronic infections without endocarditis^[12]

• Preferred regimen: Doxycycline 200 mg PO qd or 100 mg bid for 4 weeks AND Gentamicin 3 mg/kg IV qd for the first 2 weeks

• 1.2 Endocarditis^[13]

• Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g IV q24h for 6 weeks ± Doxycycline 100 mg PO bid for 6 weeks

• 2. Bartonella elizabethae

• 2.1 Endocarditis^[13]

• Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g IV q24h for 6 weeks ± Doxycycline 100 mg PO bid for 6 weeks

• 3. Bartonella bacilliformis

• 3.1 Oroya fever

• Preferred regimen: Ciprofloxacin 500 mg PO bid for 14 days
• Note: If severe disease, add Ceftriaxone 1 g IV qd for 14 days

• 3.2 Verruga peruana^[14]

• Preferred regimen: Azithromycin 500 mg PO qd for 7 days
• Alternative regimen (1): Rifampin 600 mg PO qd for 14-21 days
• Alternative regimen (2): Ciprofloxacin 500 mg bid for 7-10 days

• 4. Bartonella henselae^[15]

• 4.1 Cat scratch disease

• No treatment recommended for typical cat scratch disease, consider treatment if there is an extensive lymphadenopathy
• 4.1.1 If extensive lymphadenopathy

• Preferred regimen (1) (pediatrics): Azithromycin 500 mg PO on day 1 THEN 250 mg PO qd on days 2 to 5
• Preferred regimen (2) (adults): Azithromycin 1 g PO at day 1 THEN 500 mg PO for 4 days

• 4.2 Endocarditis

• Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g/day IV for 6weeks ± Doxycycline 100 mg PO bid for 6 weeks

• 4.3 Retinitis

• Preferred regimen: Doxycycline 100 mg bid AND Rifampin 300 mg bid PO for 4-6 weeks

• 4.4 Bacillary angiomatosis^[16]

• Preferred regimen (1): Erythromycin 500 mg PO qid for 2 months at least
• Preferred regimen (2): Doxycycline 100 mg PO bid for 2 months at least

• 4.5 Bacillary Pelliosis^[16]

• Preferred regimen (1): Erythromycin 500 mg PO qid for 4 months at least
• Preferred regimen (2): Doxycycline 100 mg PO bid for 4 months at least

qu:Sirk’i

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Carrión’s disease, or Oroya fever, or Peruvian Wart is a rare infectious disease found only in Peru, Ecuador, and Colombia.^[1] It is endemic in some areas of Peru,^[2] and is caused by infection with the bacterium Bartonella bacilliformis and transmitted by sandflies of genus Lutzomyia.

Whether because rodent associated, IV transmitted or because tick borne disease is higher risk for the homeless, homeless IV drug users are at high risk for Bartonella infections, particularly B. elizabethae. B. elizabethae seropositivity rates in this population range from 12.5% in Los Angeles,^[3] to 33% in Baltimore, Maryland,^[4] 46% in New York,^[5] and in Sweden 39%.^[6]

Cat scratch disease is a worldwide disease.

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