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Human bartonellosis is the clinical term to define the bacterial infections by the genus Bartonella species. They can cause long recognized diseases, such as Carrion´s disease, Trench fever, CSD (Cat Scratch Disease), and other recognized diseases, such as BA (Bacillary Angiomatosis), Peliosis Hepatis, chronic bacteremia, endocarditis, chronic lymphadenopathy, and neurological disorders.
- Carrion´s disease
Bartonellosis by Bartonella bacilliformis has been known since Pre-Inca times. Numerous artistic representations in clay (called "huacos")of the chronic phase have been found in endemic areas. The spanish chronist, Garcilazo De La Vega described a disease with warts in spanish troops during the conquest of Inca Empire, in Coaque-Ecuador. During a long time was thought that the disease was endemic inly in Peru and that it had only one phase, the "peruvian wart" or "verruga peruana"
In 1875 an outbreak, characterized by fever and anemia ("oroya fever") occurred in the region of construction of the railroad line between Lima and Oroya. In August 1885, Daniel A. Carrion, a Peruvian medical student, inoculated with the help of Evaristo Chavez the material taken from a verruga lesion of a patient in chroic phase (Carmen Paredes) and after 3 weeks developed classic symptoms of the acute phase of the disease, thus establishing a common source for these 2 diseases. He died from bartonellosis the October 5th, 1885 and was recognized like a martyr of peruvian medicine and the term Carrion´s disease was used until our times (peruvian medicine day is october 5th in honor to him). Alberto Barton, a peruvian microbiologist, identified Bartonella bacilliformis within erythrocytes in 1905, an announced the discovery of the etiologic agent (Barton bacillus)in 1909, which was called Bartonella bacilliformis.
In the 1990s, with the world epidemic of AIDS, Bartonella henselae or Bartonella quintana were associated to AIDS-related bacillary angiomatosis—a disease with manifestations that often include nodular skin lesions that are similar in appearance to verruga peruana lesions. By the way, serologic, PCR, and culture data established that B. henselae was the predominant causative agent of cat-scratch disease. With PCR, Bartonella species were ientified in patients who had culture-negative endocarditis. Study of Bartonella has revealed that at least 12 Bartonella species cause disease in humans or animals.
As interest in Bartonella species has grown in recent years, and a new specie was identified in 2007 producing a "Oroya fever like syndrome" characterized by fever, anemia, and splenomegaly. The new specie has been named Bartonella rochalimae and was isolated from a traveller to Peru.
- Cat scratch disease
In 1988, English and col isolated and cultured a bacterium that was named Afipia felis in 1992. This agent was considered the etiologic agent of CSD but further studies failed to support this conclusion. Serologic studies showed and association between CSD and B.henselae, in 1992. In 1993 Dolan and col  isolated Rochalimae henselae (now called B.henselae) from the lymph nodes of patients with CSD. Also, B henselae was associated with bacteremia, bacillary angiomatosis, and peliosis hepatis in HIV patients, and bacteremia and endocarditis in immunocompetent and immunocompromised patients.
- Trench fever
Detailed descriptions of the disease were reported in soldiers during the World War I. Also known as 5-day fever or quintan fever or Wolhinie fever. Actually this disease is known as "urban trench fever" because is described in homeless and alcoholics people.
Bartonella bacilliformis has been found only in Peru, Ecuador and Colombia. Geographic and weather conditions vary depending of the region and emergence or re-emergence of several infectious diseases including bartonellosis, seem to coincide with "el Niño" weather phenomena. Bartonellosis is endemic in some areas of Peru and epidemic outbreaks of the disease have been identified in new areas after "el Niño", not only in the Andes but in jungle. The mortality rate during outbreaks is high. No cases of chronic phase are found in epidemic areas and no animal reservoir has been identified until now in epidemic and endemic areas. Weather changes, migrations of the populations and other non-identified factors can explain the change in the epidemiology of the disease.
Bartonella henselae is globally endemic. Serologic studies indicate that infection of domestic cats is worldwide and bacteremia has been documented in healthy domestic cats that have been associated with bacillary angiomatosis or cat scratch disease in their human contacts.
Bartonella quintana was described in soldiers during the World War I. Actually is endemic in homeless and alcoholic people.
Phlebotomine sand flies of the genus Lutzomyas are the suspected vectors of Bartonella bacilliformis. They are smaller than a mosquito, larger than a midge and colloration varies from light brown (sandy or fawn) to gray or black. They require humid, not wet, conditions to live (mainly in tropics and subtropics). Only females sand flies take a blood meal and have nocturnal feeding behavior. The sand flies are weak fliers, travel in short hops rather than in sustained flight and they fly only at night unless disturbed in their daytime resting site.
The distribution of Carrion’s disease and Lutzomyia verrucarum is different in epidemic areas. In other areas is not possible to find Lutzomya verrucarum. Another suspected vector is Lutzomyia peruensis
Cat fleas of the genus Ctenocephalides felis are the vector of Bartonella henselae. Fleas appear to be the primary vector for cat-to-cat transmission. Bartonella clarridgeiae causes asymptomatic infection in cats and may be capable of occasional transmission to humans and produce human bartonellosis.
The human body louse of the genus Pediculus humanus corporis are the vector of Bartonella quintana.
Members of the genus Bartonella are facultative intracellular bacteria, alpha 2 subgroup Proteobacteria. The genus comprises B.bacilliformis, species of the former genera Rochalimae and Grahamella and new species recently described:
|B.bacilliformis||human||Carrion disease/Verruga peruana|
|B.quintana||human||Trench fever, bacteremia, bacillary angiomatosis, endocarditis|
|B.henselae||cats||Cat scratch disease, bacillary angiomatosis, bacteremia, endocarditis, aseptic meningitis, Parinaud´s syndrome, Peliosis hepatis|
|B.rochalimae||human||Carrion disease like syndrome|
In mammals, each Bartonella species is highly adapted to its reservoir host as the result of intracellular parasitism and can persist ni the bloodstream of the host. Intraerythrocytic parasitism is only observed in the acute phase of Carrion´s disease. Bartonella also have a tropism for endothelial cells, observed in the chronic phase of Carrion´s disease (also known as Verruga peruana) and Bacillary angiomatosis. Pathological response can varies 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 (BA in immunocompromised patients), endocarditis or meningitis. Some of the diseases can resolve spontaneously without treatment.
In the case of Bartonella bacilliformis, is transmitted by the bite of the suspected vector Lutzomyia spp. Following the transmission, bacteria infect red blood cell and endothelial cells. The physical damage and bartonella antigens in the membranes of the red blood cells stimulate the Reticuloendothelial System to produce an intense erythrophagocytosis by macrophages and histiocytic cells resulting in severe extravascular hemolytic anemia. The first step in the process is bacterial adhesion, interacting through multiple surface-exposed membrane proteins. The second step is the production of the extra cellular protein, termed deformin, that produces deep invaginations within the erythrocyt membrane. The third step is the motility of the multiple unipolar flagella. Finally, the red blood cell surface becomes markedly deformed with trenches, conic depressions and hole-like depressions. Important genetic determinant is the invasion-associated locus (ial) which is a putative virulence determinant implicated in the invasion process. The invasion of endothelial cells is an active process dependent on the activation of Rho, which is an intracellular signalimplicated in the rearrangement of the host cell actin cytoskeletal network. Following invasion, endothelial cell proliferation starts, but the exact mechanism responsible for this proliferation remains undetermined. The angiogenic factor is mitogenic for endothelil cells in vitro and can cause angiogenesis in rats.
Signs and symptoms
- Carrion´s disease
The clinical symptoms of bartonellosis are pleomorphic and some patients from endemic areas may be asymptomatics. 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 that 39ºC), pallor, malaise, nonpainful hepatomegaly, jaundice, lymphadenopathy, splenomegaly. This phase is characterized by severe hemolytic anemia and transient immunosuppression. The case fatality ratios of untreated patients exceded 40% but reach around 90% when opportunistic infection with Salmonella spp 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 cutaneus rash produced by a proliferation of endothelial cells and is known as "peruvian warts" or "verruga peruana". Depending of the size and characteristics of the lesions, there are three types: miliary (1-4 mm), nodular or subdermic and mular (>5mm). Miliary lesions are the most common.
The most common findings are bleeding of verrugas, fever, malaise, arthralgias, anorexia, myalgias, pallor, lymphadeopathy, and hepato-splenomegaly.
- Cat scratch disease is characterized by a primary cutaneus papule or pustule develops about 3 to 10 days after an animal contact (kitten or feral cat) at a site of inoculation (usually a scratch or bite) and may last for 1 to 3 weeks. Regional lymphadenopathy ipsilateral to the inoculation site (head, neck or upper extremity) develops in 1 to 7 weeks. Symptoms of infection include: fever, malaise, fatigue, headache, sore throat, rash, and lymphadenopathy. Atypical presentations are Parinaud´s oculoglandular syndrome (a self-limited granulomatous conjunctivitis and ipsilateral preauricular lymphadenitis), self-limited granulomatous hepatitis and/or splenitis, atypical pneumonitis, osteitis, neurologic syndromes (mainly encephalopathy and neuroretinitis), and fever of unknown origin.
Encephalopathy usually follows the development of lymphadenopathy. Persistent, genralized headache is a common part of the history, but fever is an inconsistent finding. Symptoms include restless, seizures (focal or generalized), brief and self-limited status epilepticus. Also, acute transient neurologic manifestations include nuchal rigidity, pathologic reflexes, pupillary dilatation. Neurologic deficits such as aphasia, cranial nerve palsy, palsy, paresis, hemiplegia, and ataxia are also usually self-limited but the time of resultion may span weeks to months to as long a year. The persistance of intellectual impairment and of seizures has been reported uncommonly. Neuroretinitis is characterized by loss of visual acuity, usually unilaterally, sometimes preceded by an influenza-like syndrome or the development of unilateral lymphadenopathy. Papilledema is the most common retinal manifestation and is associated with macular exudates in a star formation. The course is benign
- Bacillary Angiomatosis is 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 diagnosis include Kaposi´s sarcoma, pyogenic granuloma, hemangioma, Verruga Peruana, subcutanous tumors. Lesions can affect bone marrow, liver, spleen or lymph nodes. B. henselae y B. quintana can cause bacillary angiomatosis.
- Peliosis hepatis is defined as a vascular proliferation of sinusoid hepatic capillaries resulting in blood-filled spaces in the liver. B.henselae is recognized as the etiologic agent in HIV patients and organ transplant recipients. Peliosis hepatis can be associated by peliosis of the spleen, as well as Bacillary angiomatosis of the skin in HIV patients.
- Trench fever, also known as 5-day fever or quintan fever, is characterized by a spectrum of self-limited clinical patterns. The incubation period is between 3 to 38 days. The first symptoms are chills and fever during 4 to 5 days, followed by febrile paroxysms, each lasting about 5 days. The continous form is manifested by 2 to 6 weeks of uninterrupted fever. Afebril infection is the least common form. Other signs and symptoms include: headache, vertigo, retroorbital pain, conjunctival injection, nystagmus, myalgias, arthralgias, hepatosplenomegaly, rash, leukocytosis, and albuminuria. In HIV-infected patients the disease is characterized by insidous development of malaise, body aches, fatigue, weight loss, progressively higher and longer recurring fevers, and sometimes headache. Hepatomegaly can be observed.
- Bartonella bacilliformis
Acute phase: the diagnosis in the acute phase can be done using the thin blood film with Giemsa stain. It is possible to observe the cocco-bacillus inside or outsie the red blood cells. Other important diagnostic tests are culture, Polymerase Chain Reaction (PCR), Immunoblot, and Immunofluorescence.
Chronic phase: the diagnosis is basically a clinic diagnosis. Bacteria can be isolated by cultures, Immunoblot, IFA, and Warthin–Starry stain of a wart biopsy.
- Bartonella henselae
- Bartonella quintana
|CSD||no recommendation||no recommendation|
|Retinitis||Doxicycline + Rifampin||unknown|
|Trench fever or chronic bacteremia by B.quintana||Doxicycline + Gentamicin||unknown|
|Bacillary angiomatosis||Erythromycin or Doxycycline||Erythromycin|
|Peliosis hepatis||Erythromycin or Doxycycline||Erythromycin|
|Endocarditis||Doxycycline + Gentamicin + Rifampin or Ceftriaxone + Gentamicin|
|Carrion´s disease (acute phase)||Ciprofloxacin or Chloramphenicol||Chloramphenicol + beta-lactam|
|Carrion´s disease (chronic phase:Verruga peruana)||Rifampin or macrolides||Rifampin or macrolides|
- Bartonellosis (Carrion's disease) in the modern era
- Human Bartonellosis caused by Bartonella bacilliformis
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