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Bartonellosis is an infectious disease produced by bacteria of the genus Bartonella . [1] 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. [2]

Bacteria A domain of prokaryotes – single celled organisms without a nucleus

Bacteria are a type of biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a number of shapes, ranging from spheres to rods and spirals. Bacteria were among the first life forms to appear on Earth, and are present in most of its habitats. Bacteria inhabit soil, water, acidic hot springs, radioactive waste, and the deep portions of Earth's crust. Bacteria also live in symbiotic and parasitic relationships with plants and animals. Most bacteria have not been characterised, and only about half of the bacterial phyla have species that can be grown in the laboratory. The study of bacteria is known as bacteriology, a branch of microbiology.

A genus is a taxonomic rank used in the biological classification of living and fossil organisms, as well as viruses, in biology. In the hierarchy of biological classification, genus comes above species and below family. In binomial nomenclature, the genus name forms the first part of the binomial species name for each species within the genus.

<i>Bartonella</i> genus of bacteria

Bartonella is a genus of Gram-negative bacteria. It is the only genus in the family Bartonellaceae. Facultative intracellular parasites, Bartonella species can infect healthy people, but are considered especially important as opportunistic pathogens. Bartonella species are transmitted by vectors such as ticks, fleas, sand flies, and mosquitoes. At least eight Bartonella species or subspecies are known to infect humans.



Carrión's disease

Patients can develop two clinical phases: an acute septic phase and a chronic eruptive phase associated with skin lesions. [3] 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 .

Dermatology field of medicine dealing with the hair, nails, skin and its diseases

Dermatology is the branch of medicine dealing with the skin, nails, hair and its diseases. It is a specialty with both medical and surgical aspects. A dermatologist is specialist doctor that manages diseases, in the widest sense, and some cosmetic problems of the skin, hair and nails.

Fever common medical sign characterized by elevated body temperature

Fever, also known as pyrexia and febrile response, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using values between 37.5 and 38.3 °C. The increase in set point triggers increased muscle contractions and causes a feeling of cold. This results in greater heat production and efforts to conserve heat. When the set point temperature returns to normal, a person feels hot, becomes flushed, and may begin to sweat. Rarely a fever may trigger a febrile seizure. This is more common in young children. Fevers do not typically go higher than 41 to 42 °C.

Red blood cell most common type of blood cell

Red blood cells, also known as RBCs, red cells, red blood corpuscles, haematids, erythroid cells or erythrocytes (from Greek erythros for "red" and kytos for "hollow vessel", with -cyte translated as "cell" in modern usage), are the most common type of blood cell and the vertebrate's principal means of delivering oxygen (O2) to the body tissues—via blood flow through the circulatory system. RBCs take up oxygen in the lungs, or gills of fish, and release it into tissues while squeezing through the body's capillaries.

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).

In medicine, nodules are solid, elevated areas of tissue or fluid inside or under the skin with a diameter greater than 0.5 centimeters. Nodules may form on tendons and muscles in response to injury. The vocal cords may also develop nodules. Nodules are normally benign and often painless, although they can affect the functioning of the organ.

Angioma Wikimedia category

Angiomas are benign tumors derived from cells of the vascular or lymphatic vessel walls (endothelium) or derived from cells of the tissues surrounding these vessels.

Cat-scratch disease

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. [4] [5]

Axilla area of human body beneath joint between arm and torso

The axilla is the area on the human body directly under the joint where the arm connects to the shoulder. It also provides the under-arm sweat gland.

In human anatomy, the groin is the junctional area between the abdomen and the thigh on either side of the pubic bone. This is also known as the medial compartment of the thigh that consists of the adductor muscles of the hip or the groin muscles. A pulled groin muscle usually refers to a painful injury sustained by straining the hip adductor muscles.

Neck part of the body, on many terrestrial or secondarily aquatic vertebrates, that distinguishes the head from the torso or trunk

The neck is the part of the body, on many vertebrates, that separates the head from the torso. It contains blood vessels and nerves that supply structures in the head to the body. These in humans include part of the esophagus, the larynx, trachea, and thyroid gland, major blood vessels including the carotid arteries and jugular veins, and the top part of the spinal cord.

B. henselae can be associated with bacteremia, bacillary angiomatosis, and peliosis hepatis in HIV patients, and bacteremia and endocarditis in immunocompetent and immunocompromised patients. [6] 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. [7] Disease progression may be accelerated if the host is subsequently infected by an immune-suppressing virus such as Epstein Barr virus. [8]

HIV human retrovirus, cause of AIDS

The human immunodeficiency viruses (HIV) are two species of Lentivirus that causes HIV infection and over time acquired immunodeficiency syndrome (AIDS). AIDS is a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype. In most cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of blood, pre-ejaculate, semen, and vaginal fluids. Non-sexual transmission can occur from an infected mother to her infant during pregnancy, during childbirth by exposure to her blood or vaginal fluid, and through breast milk. Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells.

Bacillary angiomatosis

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. [9] Severe, progressive and disseminated disease may occur in HIV patients. [10] Differential diagnoses include Kaposi´s sarcoma, pyogenic granuloma, hemangioma, verruga Peruana, and subcutanous tumors. Lesions can affect bone marrow, liver, spleen, or lymph nodes.

Blood vessel a tubular structure which carries blood

The blood vessels are the part of the circulatory system, and microcirculation, that transports blood throughout the human body. These vessels are designed to transport nutrients and oxygen to the tissues of the body. They also take waste and carbon dioxide and carry them away from the tissues and back to the heart. Blood vessels are needed to sustain life as all of the body’s tissues rely on their functionality.There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and the tissues; and the veins, which carry blood from the capillaries back toward the heart. The word vascular, meaning relating to the blood vessels, is derived from the Latin vas, meaning vessel. Some structures -- such as cartilage, the epithelium, and the lens and cornea of the eye -- do not contain blood vessels and are labeled avascular.

Kaposis sarcoma connective tissue cancer

Kaposi's sarcoma (KS) is a type of cancer that can form masses in the skin, lymph nodes, or other organs. The skin lesions are usually purple in color. They can occur singularly, in a limited area, or be widespread. It may worsen either gradually or quickly. Lesions may be flat or raised. Human herpesvirus 8 (HHV8) is found in the lesions of all those who are affected. Risk factors include poor immune function, either as a result of disease or specific medications, and chronic lymphedema.

Granuloma inflammation consisting of immune cells known as macrophages

A granuloma is a structure formed during inflammation that is found in many diseases. It is a collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances it perceives as foreign but is unable to eliminate. Such substances include infectious organisms including bacteria and fungi, as well as other materials such as keratin and suture fragments.

Peliosis hepatis

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. [11]

Trench fever

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. [12]


Members of the genus Bartonella are facultative intracellular bacteria, alpha 2 subgroup Proteobacteria. The genus comprises:

Bartonella speciesReservoirDisease
Bartonella bacilliformis humanCarrion's disease/verruga Peruana
Bartonella quintana humanTrench fever, bacteremia, bacillary angiomatosis, endocarditis
Bartonella henselae catsCat-scratch disease, bacillary angiomatosis, bacteremia, endocarditis, encephalitis, meningitis
Bartonella elizabethae ratsEndocarditis
Bartonella grahamii Retinitis
Bartonella vinsoni dogsEndocarditis], bacteremia
Bartonella washonsis rodents Myocarditis
Bartonella clarridgiae catsBacteremia
Bartonella rochalimae humanCarrion´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. [13] 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. [13] [14] The CDC does not recommend lymph node aspiration for diagnostic purposes. [13]

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. [14] [15] [16] IFA can generally be used to confirm a diagnosis of Bartonella infection, but is limited by antibody cross-reactivity with other bacteria species [13] [14] which can cause a false positive, and antigen variability which can result in false negatives. [14] [17]

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. [14] [15] [16] [17] IFA sensitivity may range from 14-100%, [14] causing discrepancies between PCR and serology test results. [17] 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%). [14] Western blot for protein detection of Bartonella-associated proteins has also been reported, but this method does not show clear immunoreactive profiles. [14]


The CDC states that PCR testing from a single blood draw is not sufficiently sensitive for B.henselae testing, [13] and can result in high false negative rates [17] due to a small sample volume and levels below the limit of molecular detection. [14]

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. [13] [17] [18] [19] [20] 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. [13] [17] [21]

Enrichment Culture

Bartonella growth rates improve when cultured in an enrichment inoculation step in a liquid insect-based medium [18] [21] [22] such as Bartonella α-Proteobacteria Growth Medium (BAPGM) [17] or Schneider’s Drosophila-based insect powder medium. [21] [22] 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. [21] [22] Insect-based liquid media supports the growth and co-culturing of at least seven Bartonella species, [14] [17] [21] [22] reduces bacterial culturing time and facilitates PCR detection and isolation of Bartonella spp. from animal and patient samples. [14] [17] [19] 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. [17] 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. [19] [23]

Serial Testing

As Bartonella spp. infect at low levels and cycle between blood and tissues, [18] multiple blood draws over time may be necessary to detect infection. [24]


Treatment of infections caused by Bartonella species include: [25] [26]

Cat-scratch diseaseAzithromycin + RifampinUnknown
Retinitis Doxycycline + rifampinunknown
Trench fever or chronic bacteremia by B. quintanaDoxycycline + gentamicinunknown
Bacillary angiomatosisErythromycin or doxycyclineErythromycin
Peliosis hepatisErythromycin or doxycyclineErythromycin
EndocarditisDoxycycline + gentamicin + rifampin or ceftriaxone + gentamicin
Carrión's disease (acute phase)Ciprofloxacin or chloramphenicolChloramphenicol + beta-lactam
Carrión's disease (chronic phase)Rifampin or macrolidesRifampin or macrolides

Some authorities recommend the use of azithromycin. [27]


Carrión's disease, or Oroya fever, or Peruvian wart is a rare infectious disease found only in Peru, Ecuador, and Colombia. [28] It is endemic in some areas of Peru, [29] 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 . [30] 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. [31] 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. [32]

History of discovery

Carrión's disease

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 laterOctober 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. [33]


In 1988, English et al. [34] 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 [35] 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. [36]

Trench fever

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 . [37]

Related Research Articles

Trench fever is a moderately serious disease transmitted by body lice. It infected armies in Flanders, France, Poland, Galicia, Italy, Salonika, Macedonia, Mesopotamia, Russia and Egypt in World War I. Three noted sufferers during WWI were the authors J. R. R. Tolkien, A. A. Milne, and C. S. Lewis. From 1915 to 1918 between one-fifth and one-third of all British troops reported ill had trench fever while about one-fifth of ill German and Austrian troops had the disease. The disease persists among the homeless. Outbreaks have been documented, for example, in Seattle and Baltimore in the United States among injection drug users and in Marseille, France, and Burundi.

Babesiosis malaria-like parasitic disease caused by infection with Babesia, a genus of Apicomplexa

Babesiosis is a malaria-like parasitic disease caused by infection with Babesia, a type of Apicomplexa. Human babesiosis transmission via tick bite is most common in the Northeastern and Midwestern United States and parts of Europe, and sporadic throughout the rest of the world. It occurs in warm weather. People can get infected with Babesia parasites by the bite of an infected tick, by getting a blood transfusion from an infected donor of blood products, or by congenital transmission. Ticks transmit the human strain of babesiosis, so it often presents with other tick-borne illnesses such as Lyme disease. After trypanosomes, Babesia is thought to be the second-most common blood parasite of mammals, and they can have a major impact on health of domestic animals in areas without severe winters. In cattle the disease is known as Texas cattle fever, redwater, or piroplasmosis.

<i>Bartonella henselae</i> species of bacterium

Bartonella henselae, formerly Rochalimæa, is a proteobacterium that is the causative agent of cat-scratch disease (bartonellosis).

Carrions disease infectious disease produced by Bartonella bacilliformis infection

Oroya fever or Carrion's disease is an infectious disease produced by Bartonella bacilliformis infection.

Bacillary angiomatosis human disease

Bacillary angiomatosis (BA) is a form of angiomatosis associated with bacteria of the genus Bartonella.

<i>Sporothrix schenckii</i> species of fungus

Sporothrix schenckii is a fungus that can be found worldwide in the environment. The species is present in soil as well as in and on living and decomposing plant material such as peat moss. It can infect humans as well as animals and is the causative agent of sporotrichosis, commonly known as "rose handler's disease". The most common route of infection is the introduction of spores to the body through a cut or puncture wound in the skin. Infection commonly occurs in otherwise healthy individuals but is rarely life-threatening and can be treated with antifungals. In the environment it is found growing as filamentous hyphae. In host tissue it is found as a yeast. The transition between the hyphal and yeast forms is temperature dependent making S. schenckii a thermally dimorphic fungus.

A rickettsiosis is a disease caused by intracellular bacteria.

Peliosis hepatis is an uncommon vascular condition characterised by multiple, randomly distributed, blood-filled cavities throughout the liver. The size of the cavities usually ranges between a few millimetres and 3 cm in diameter. In the past, it was a mere histological curiosity occasionally found at autopsies, but has been increasingly recognised with wide-ranging conditions from AIDS to the use of anabolic steroids. It also occasionally affects spleen, lymph nodes, lungs, kidneys, adrenal glands, bone marrow, and other parts of gastrointestinal tract.

Bartonella rochalimae is a recently discovered strain of Gram-negative bacteria in the genus Bartonella, isolated by researchers at the University of California, San Francisco (UCSF), Massachusetts General Hospital, and the United States Centers for Disease Control and Prevention. The bacterium is a close relative of Bartonella quintana, the microbe which caused trench fever in thousands of soldiers during World War I. Named after Brazilian scientist Henrique da Rocha Lima, B. rochalimae is also closely related to Bartonella henselae, a bacterium identified in the mid-1990s during the AIDS epidemic in San Francisco as the cause of cat scratch fever, which still infects more than 24,000 people in the United States each year.

Bartonella bacilliformis is a proteobacterium, Gram negative aerobic, pleomorphic, flagellated, motile, coccobacillary, 2–3 μm long, 0.2–0.5 μm wide, and a facultative intracellular bacterium.

Bartonella quintana, originally known as Rochalimaea quintana, and "Rickettsia quintana", is a micro-organism transmitted by the human body louse. This microorganism is the causative agent of the well known trench fever. This bacterium caused outbreaks of trench fever affecting 1 million soldiers in Europe during World War I.

Ehrlichiosis ewingii infection is an infectious disease caused by an intracellular bacteria, Ehrlichia ewingii. The infection is transmitted to humans by the tick, Amblyomma americanum. This tick can also transmit Ehrlichia chaffeensis, the bacteria that causes human monocytic ehrlichiosis (HME).

Bacillary peliosis is a form of peliosis hepatis that has been associated with bacteria in the genus Bartonella.

Didier Raoult is a French biologist. He holds MD and Ph.D. degrees and specializes in infectious diseases.

Rickettsia felis is a species of bacterium, the pathogen that causes cat-flea typhus in humans. In cats the disease is known as flea-borne spotted fever. Rickettsia felis also is regarded as the causative organism of many cases of illnesses generally classed as fevers of unknown origin in humans in Africa.

Cat-scratch disease Human disease

Cat-scratch disease (CSD) is an infectious disease that results from a scratch or bite of a cat. Symptoms typically include a non-painful bump or blister at the site of injury and painful and swollen lymph nodes. People may feel tired, have a headache, or a fever. Symptoms typically begin within 3-14 days following infection.

<i>Mycoplasma haemofelis</i> species of bacterium

Mycoplasma haemofelis is a gram negative epierythrocytic parasitic bacterium. It often appears in bloodsmears as small (0.6μm) coccoid bodies, sometimes forming short chains of 3 to 8 organisms. It is usually the causative agent of Feline Infectious Anemia (FIA) in the United States.

Legionella anisa is a Gram-negative bacterium, one of more than 40 species in the family Legionellaceae. After Legionella pneumophila, this species has been isolated most frequently from water samples. This species is also one of the several pathogenic forms of Legionella having been associated with rare clinical cases of illness including Pontiac fever and Legionnaires' disease.

Bartonella koehlerae is a proteobacterium first isolated from cats. Its genome consists of 1.7-1.8 Mb.


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