eMedicine Specialties > Infectious Diseases > Bacterial Infections

Bartonellosis

Author: Kassem A Hammoud, MD, Fellow, Department of Internal Medicine, Division of Infectious Diseases, University of Kansas Medical Center
Coauthor(s): Daniel Hinthorn, MD, Director, Division of Infectious Diseases, Professor, Departments of Internal Medicine, Pediatrics and Family Medicine, University of Kansas; Brian Edwards, MD, Consulting Staff, Department of Infectious Diseases, Cotton O'Neil Clinic
Contributor Information and Disclosures

Updated: Oct 13, 2008

Introduction

Background

Bartonellosis comprises infections caused by newly emerging pathogens in the genus Bartonella. In 1909, A. L. Barton described organisms that adhered to RBCs. The name Bartonia, later Bartonella bacilliformis, was used for the only member of the group identified before 1993. Rochalimaea (named for Rocha-Lima), a similar group, were recently combined with Bartonella. Although these organisms were originally thought to be rickettsiae, Bartonella bacteria can be grown on artificial media, unlike rickettsiae.

At least a dozen species belong to the genus Bartonella. Three Bartonella species are currently considered important causes of human disease, but other significant human pathogens in this genus will undoubtedly be found in the future. In one study, serum specimens from 114 patients hospitalized with a febrile illness were tested with an indirect immunofluorescence assay (IFA) using rodent and human Bartonella pathogens; 5 patients had high-titer seroconversion to rodent-associated Bartonella.¹

B bacilliformis causes Oroya fever and verruga peruana. Bartonella henselae causes catscratch disease (CSD) and peliosis of the liver (often called bacillary peliosis). Bartonella quintana causes trench fever. Both B henselae and B quintana may cause bacillary angiomatosis, infections in homeless populations, and infections in patients infected with HIV.

New Bartonella species that may cause human disease include Bartonella vinsonii, Bartonella clarridgeiae, Bartonella tamiae, Bartonella rochalimae, and Bartonella elizabethae. Several of these other species are found in animals.

For additional information on emerging and reemerging infectious diseases, see Medscape’s Emerging and Reemerging Infectious Diseases Resource Center.

Pathophysiology

B bacilliformis, which uses a polar flagellum for motility, adheres to and invades RBCs. After entry, the organism replicates in vacuoles. This species also makes an endothelial cell–stimulating factor that causes proliferation of both endothelial cells and blood vessels.

B henselae and B quintana do not bind to intact human erythrocytes in the same way that B bacilliformis does; however, these organisms make a protein binder that adheres to feline RBC membranes, and they penetrate into endothelial cells. Both species also initiate production of an endothelial cell–stimulating factor. Because lysis-centrifugation blood cultures show enhanced isolation of B henselae and B quintana, intracellular forms are most likely present in humans. Erythrocytes may serve as a reservoir for Bartonella species.

B quintana also invades endothelial cells and forms bacterial aggregates that are taken internally by the invasome, a unique phagosomal structure.² These proliferate and make intracellular blebs.

Frequency

United States

Catscratch disease caused by B henselae infection occurs in approximately 1 per 10,000 persons.

B quintana is found worldwide and causes febrile outbreaks. Poor sanitation and lack of personal hygiene strongly correlate with transmission by the body louse Pediculus humanus. B quintana is emerging as a recognized cause of disease among homeless persons and persons with AIDS. Trench fever syndrome is found among people with alcoholism and those who are homeless. Persons who are indigent in inner-city Seattle were evaluated for antibodies to B quintana. Approximately 20% of these people had antibody titers of 1:64 or greater; in comparison, this titer was found in only 2% of blood donors.³

International

B bacilliformis transmission is limited to the Andes Mountains at elevations of 1000-3000 meters because of the habitat of the sand fly Phlebotomus, now called Lutzomyia. Outbreaks of B bacilliformis infection occur only in the Andes. Cases elsewhere in the world are found in travelers.

B henselae is found throughout the world in association with both domestic and feral cats. It has recently been reported in cats in Germany. The cat flea Ctenocephalides felis is an arthropod vector. B henselae has been isolated from ticks, but their competence in disease transmission is unclear.^4,5

B quintana infection has been reported in 16% of homeless hospitalized patients in France.

Other species, such as B clarridgeiae, may be a cause of asymptomatic infection in cats.

Mortality/Morbidity

Catscratch disease usually causes self-limited regional adenopathy. Acute hemiplegia has been reported in an 11-year-old boy.⁶ Encephalopathy is the most common neurologic complication but is rare.

B henselae is a common cause of culture-negative endocarditis. Valve replacement is required in approximately 80% of cases, but overall prognosis is good, with survival rates in excess of 80%.⁷ In a 2003 article in Medicine by Houpikian and Raoult, Bartonella endocarditis was associated with B quintana in 75% of cases and with B henselae in 25% of cases. They reported a mortality rate of 7% among 99 patients with Bartonella endocarditis.⁸

Trench fever is a self-limited relapsing febrile illness. Affected persons regularly recover, even without treatment. Liver abscesses and spleen abscesses in the absence of endocarditis in an immunocompetent host have been described.⁹

Disseminated forms of bartonellosis develop in patients infected with HIV. Bacillary angiomatosis and culture-negative endocarditis are caused by B henselae and B quintana. Peliosis hepatis is caused by B henselae.

Carrión disease commonly affects the pediatric population in Peru and Ecuador. Mortality and morbidity of the acute phase vary because of superimposed infections and other complications. Mortality rates associated with the eruptive phase, known as Peruvian wart, are extremely low.¹⁰

Clinical

History

Currently, Bartonella species cause several clinical syndromes, including catscratch disease (with enlarged nodes and other organ involvement), bacteremia, endocarditis, bacillary angiomatosis, peliosis hepatis, Oroya fever, and verruga peruana. The inability to mount an immune response contributes to manifestations observed in immunosuppressed individuals with advanced AIDS and other diseases.

• Catscratch disease
  • Most affected individuals have typical catscratch disease symptoms and present with an enlarged lymph node.
  • A primary inoculation lesion often develops at the site of a bite or scratch.
  • A papule or pustule develops 5-10 days after exposure. This lesion may persist for a few weeks.
  • B henselae DNA may be chronically shed into peripheral blood during the natural course of catscratch disease.¹¹
• Bacteremia and systemic illnesses
  • Trench fever was described in military personnel during World War I. Urban trench fever is now observed in homeless persons in the United States and Europe.
  • Symptoms of trench fever begin with chills and fever after an incubation period of a few days to a month. Occasionally, the patient experiences only a single febrile episode that lasts 4 or 5 days. More commonly, several episodes of fever occur. Each episode lasts about 5 days, which is the origin of the designation quintana. The patient cycles between severe chills and profuse sweating. In other patients, continuous fever lasts 2-6 weeks.
  • Associated symptoms include joint and muscle aches, injected conjunctivae, headache, dizziness, and pain behind the eyes. Some patients have diffuse symptoms without fever.
  • Some cases of trench fever become chronic with debility, with or without fever or aching, and occasionally with hyperexcitability.
  • In patients with HIV, infection with either B henselae or B quintana causes gradual onset of aching, headache, fatigue, and weight loss. Fever begins later. Persistent bacteremia with B henselae may develop in people with AIDS.
  • Encephalopathy has been associated mostly with B henselae. Guillain-Barré syndrome, hydrocephalus, and encephalopathy were associated with B quintana acute infection in one case report.¹²
• Bacillary angiomatosis and peliosis hepatitis
  • Bacillary angiomatosis was initially described in persons infected with HIV. Typically, it involved the skin and was believed to resemble Kaposi sarcoma but can affect other organs such as the respiratory tract, bone, lymph nodes, gastrointestinal tract, and brain. When the liver or spleen was involved, bacillary peliosis or peliosis hepatis was diagnosed before Bartonella infection was discovered to be the cause.
  • Symptoms depend on the anatomic site involved and may include fever, tender lymphadenopathy, and skin lesions.
• Oroya fever and verruga peruana
  • Over a century ago, a medical student named Daniel Carrión injected himself with blood from the skin lesion of a patient who had verruga peruana. He developed Oroya fever. Today, Oroya fever and verruga peruana are called Carrión disease. Prior to that time, the relationship between the diseases was unknown.
  • Bacteremia of Oroya fever begins 3-12 weeks after a bite from an infected sand fly. The illness may range from mild to very severe. In severe cases, fever, chills, headache, sweating, aches, dyspnea, mental status changes, and seizure may occur. Severe disease has an abrupt onset.

Physical

• Catscratch disease
  • Enlarged lymph glands develop 1 week to 2 months after exposure. Swollen tender nodes are the usual presenting symptom.
  • Careful examination of the interdigital spaces, skin creases, and scalp increases the chance of finding the primary inoculation lesion. Inoculation sites other than the skin include the eye and mucous membranes (oral ulcer).
  • One third to two thirds of patients develop low-grade fever that lasts several days.
  • B henselae infection is one of the common causes of fever of unknown origin and prolonged fever in children. One study showed that the absence of lymphadenopathy in patients with catscratch disease was closely related to the presence of prolonged fever or systemic complications. Another study of 186 patients with a serological diagnosis of catscratch disease showed that 30 (16.1%) patients had no regional lymphadenopathy. These patients had persistent fever and more frequent systemic complications than patients with lymphadenopathy.¹³
  • Malaise and fatigue are common. Many patients feel healthy except for the enlarged node or nodes. Patients occasionally have multifocal lymphadenopathy.
  • Laboratory studies include the following:
    • Diagnosis should be confirmed with demonstration of a 4-fold rise in antibody levels, initially immunoglobulin M (IgM) followed by immunoglobulin G (IgG).
    • Culture confirmation is difficult; PCR is more sensitive.
    • In some patients, hypercalcemia complicates catscratch disease lymphadenopathy via overproduction of vitamin D due to granuloma formation.
  • Other morbidities include the following:
    • Rarely, catscratch disease spreads and causes granulomatous hepatitis or granulomas in the spleen or bones. Granulomas in the liver or spleen do not enhance with contrast on CT scanning.
    • Parinaud oculoglandular syndrome follows contamination of the eye, often from the patient's own hand. A granulomatous conjunctivitis follows and is associated with enlarged preauricular nodes.
    • Encephalopathy is an infrequent but important manifestation that occurs in as many as 2-4% of patients with catscratch disease. Several hundred such cases probably occur in the United States each year. Manifestations include generalized headaches, restlessness, combativeness, seizure, and neurologic defects such as aphasia, cranial nerve palsy, Brown-Sequard syndrome, and ataxia. Persistent intellectual impairment has been reported. Cerebral spinal fluid (CSF) cultures and routine studies are not helpful in diagnosis.
    • In neuroretinitis caused by B henselae, a sudden loss of eyesight may be the presenting symptom. The patient usually has a prior flulike syndrome or enlarged nodes. A common examination finding is papilledema with a starburst appearance. A recent report described a 10-year-old girl with catscratch disease who developed a macular hole 12 days after presentation with neuroretinitis in association with a posterior vitreous detachment.¹⁴ Neuroretinitis is usually confirmed based on titers, but, on occasion, retinal biopsy with histopathology may prove helpful. Neuroretinitis usually resolves spontaneously except in immunocompromised patients. Multifocal chorioretinal lesions have also been described.¹⁵
    • Transverse myelitis was described in 3 patients with catscratch diseases.¹⁶ One case report described a 40-year-old patient with chronic vasculitis and polyneuropathy associated with bartonellosis.¹⁷
    • Osteomyelitis is a rare manifestation, occurring in 0.2%–0.3% of patients with catscratch disease. Medical therapy with antibiotics is very effective. Maman et al found that, among 913 patients with catscratch disease, 10.5% had musculoskeletal manifestations (myalgia, arthralgia/arthritis, neuralgia, tendinitis, osteomyelitis).¹⁸
• Bacteremia
  • Findings include injected conjunctivae, nystagmus, hepatosplenomegaly, lymphadenopathy, and a maculopapular rash.
  • Muscles or joints may be tender.
  • Laboratory studies include the following:
    • Patients typically exhibit increased leukocytes with occasional thrombocytopenia or albuminuria. Bacteremia is not usually detected.
    • Patients with prolonged bacteremia may have culture-negative endocarditis because Bartonella species do not grow on standard blood culture media. Special media must be used. B henselae and B quintana infections can cause culture-negative endocarditis. Bartonella alsatica was isolated from the valve of a patient with endocarditis.¹⁹ Most cases of Bartonella endocarditis involve native valves, but infection of prosthetic valves is possible.²⁰
    • Antibody titers are helpful in confirming the diagnosis.
  • As expected, persons with alcoholism and those who are homeless typically develop B quintana endocarditis (75% of cases), while persons with exposure to cats are more likely to harbor B henselae (25% of cases). Other Bartonella species are rarely implicated. Although many children are frequently exposed to cats, even those with catscratch disease rarely develop Bartonella endocarditis.
• Bacillary angiomatosis and peliosis hepatitis
  • Examination findings include purple to red-black, raised, palpable skin lesions.
  • When the liver, lymph node, or spleen is involved, it may be enlarged.
  • Laboratory studies include the following:
    • Patients should undergo HIV antibody testing and CD4⁺ lymphocyte assessment.
    • Patients typically have anemia and elevated levels of serum alkaline phosphatase.
• Oroya fever and verruga peruana
  • Untreated patients have a high case-fatality rate. Survivors may be more susceptible to salmonellosis or toxoplasmosis during the convalescent period.
  • Verruga peruana lesions develop as crops with onset weeks to months later in untreated survivors. These lesions begin as small nodules and subsequently grow. Highly vascular mulaire lesions then form and begin to ulcerate, bleed, and heal via fibrosis over several months. Various stages of small to larger nodules, mulaire lesions, and fibrosis may occur simultaneously.
  • Laboratory studies include the following:
    • Hemolytic anemia, thrombocytopenia, and elevated values on liver function studies are common.
    • Survivors may develop persistent bacteremia.

Causes

• Catscratch disease
  • In the United States, catscratch disease is the most common type of bartonellosis.
  • The clinical syndrome has been recognized for more than a century, but the etiology of this condition was confirmed only in the past decade. Confirmation involved isolating Bartonella species from cats and their fleas, showing an antibody titer rise in patients with the disease, and demonstrating the presence of organisms in biopsy samples through culture and PCR.
  • Occasional cases are negative for B henselae antibodies. In these instances, rare causes of catscratch disease such as B clarridgeiae or Afipia felis should be considered.
• Bacteremia may occur with either B henselae or B quintana infection and may result in disseminated diseases. Other species of Bartonella have occasionally been associated with bacteremia.
• Oroya fever and verruga peruana are manifestations of B bacilliformis infection. These diseases are not found in the United States, but they are common in the Peruvian Andes. Verruga peruana is characterized by subcutaneous nodules consisting of neovascularization, somewhat similar to bacillary angiomatosis.

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