Bartonellosis

Bartonella are Gram-negative bacteria and are facultative intracellular parasites.

• They are found in various vertebrates, rodents and their flea vectors, and are associated with an increasing range of diseases.
• Transmission is generally considered to be by arthropod vectors.
• Three species of the genus Bartonella are known to be important causes of human disease, although other species are increasingly being recognised as important.¹
• The range of infection varies from mild lymphadenopathy seen in cat scratch disease, to life-threatening systemic disease in immunocompromised patients.²
• Infections caused by Bartonella species include:
  • Cat-scratch disease: B. henselae
  • Bacillary angiomatosis: disseminated form of B. henselae infection, found most commonly in HIV-positive patients
  • Oroya fever/verruga peruana: B. bacilliformis
  • Trench fever: B. quintana; louse-borne, variable fever with persisting severe shin and other bone pain
• Endocarditis is sometimes associated with Bartonella infection (including B. henselae, B. quintana, B. elizabethae). Homelessness and alcoholism are risk factors for B. henselae endocarditis.
• Bartonella encephalopathies are rare in patients with normal immunity but may occur in HIV-positive patients, especially with B. henselae and B. quintana infection. Features include meningoencephalitis, encephalopathy and neuropsychiatric disorders.
• B. henselae osteomyelitis and hepatitis have been reported.

Synonym: Petzetakis disease (cat scratch disease without ocular granuloma or conjunctivitis).

• Epidemiology:
  • It is caused by B. henselae which is found throughout the world in association with both domestic cats (20% infected with any of 5 different species: henselae, clarridgeiae, koehlerae, weissii, and elizabethae) and wild cats.
  • Transmission is by cat bites or scratches, though the cat flea Ctenocephalides felis, may be an additional vector.
• Presentation:
  • A papule or pustule develops at the site of a bite or scratch 5-10 days after exposure, and this may persist for a few weeks.
  • Enlarged tender lymph glands develop 1 week to 2 months after exposure.
  • Fever, malaise and fatigue are common, although many patients feel healthy except for the enlarged nodes.
• Differential Diagnosis:
  • Other causes of enlarged lymph nodes, such as localized infections with regional node swelling and systemic diseases, e.g. lymphoma, leukaemia or tuberculosis.
• Investigations:
  • Serology testing is the most cost-effective method to confirm the diagnosis.
• Management:
  • Cat scratch disease is usually self-limiting and only supportive management is required.³
  • However it is usually treated with antibiotics because early treatment is believed to reduce the possibility of complications.
  • Azithromycin, erythromycin and doxycycline are all effective first-line options.⁴
• Complications:
  • Rarely spreads to cause granulomatous hepatitis or granulomas in the spleen or bones. Encephalopathy occurs infrequently.
  • Ocular involvement in 5-10% patients, with Parinaud's oculoglandular syndrome being the commonest. This is characterised by regional lymphadenopathy with conjunctivitis, retrotarsal granulations and fever.
  • Neuroretinitis may occur with sudden loss of eyesight but usually resolves spontaneously except in immunocompromised patients.
• Prognosis:
  • Rarely results in neurological sequelae.
  • Adenopathy may persist for up to two years.

Synonyms: Shinbone fever, 5-day fever, Wolhynia fever, Quintana fever, His-Werner disease.

• Epidemiology:
  • It is caused by B. quintana (formerly Rochalimaea or Rickettsia quintana.)
  • Urban trench fever is now seen in alcoholics and the homeless.
  • Poor sanitation and lack of personal hygiene strongly correlate with transmission by the body louse Pediculus humanus.
• Presentation:
  • Fever develops after an incubation period of a few days to a month. Usually, several episodes of fever develop and each episode lasts about 5 days.
  • Other symptoms include joint and muscle aches, headache, dizziness, and pain behind the eyes. Some patients have diffuse symptoms without fever.
  • May cause culture-negative endocarditis.
  • On examination there are injected conjunctivae, nystagmus, hepatosplenomegaly, lymphadenopathy, a maculopapular rash and tender muscles and joints.
• Differential Diagnosis:
  Other causes of fever, headache, focal neurology and lymphadenopathy, e.g. CMV, HIV seroconversion.
  • Other causes of culture-negative endocarditis include Legionellosis, Q Fever and slow-growing streptococci.
• Investigations:
  • Serology testing is the most cost-effective method to confirm the diagnosis.
  • Culture for Bartonella may be useful in patients who have other manifestations of either B henselae or B quintana infection (e.g. fever of unknown origin, neuroretinitis, encephalitis, culture-negative endocarditis). Fresh media is required to increase the chance of isolating the organism.
• Management:
  • Doxycycline is given for at least two weeks and a longer course when the liver or other organs are involved. Chloramphenicol may be used in severe cases.⁴
• Complications:
  • Persistent bacteraemia with B. henselae may develop in people with AIDS.
• Prognosis:
  • Usually self-limiting. Trench fever reinfection may recur within 3-6 months, because antibodies do not give full protection.
  • Bartonella endocarditis: the recommended treatment is doxycycline for 6 weeks, with gentamicin for 2 weeks.⁴ Surgical resection of heart valves is usually required. Mortality rate of bartonella endocarditis is 30%.

• Both B. quintana and B. henselae are associated with these conditions.
• Bacillary angiomatosis was initially described in people infected with HIV infection.
• Symptoms depend on the anatomical site involved and may include fever, tender lymphadenopathy, and skin lesions. Cystic hepatitis (peliosis) often occurs in bacillary angiomatosis.
• Homeless persons and alcoholics typically develop B. quintana endocarditis.
• Presentation:
  • Lesions are often dark purple and resemble Kaposi's sarcoma.
  • There may be enlargement of the liver, lymph nodes, or spleen if infected.
• Investigations:
  • Patients should have HIV antibodies and CD4 lymphocyte counts checked.
  • Usually causes anaemia and elevated serum alkaline phosphatase.
• Management:
  • Effective antibiotics include erythromycin, doxycycline, azithromycin, clarithromycin, or a fluoroquinolone.
  • Doxycycline combined with rifampin is effective for patients with severe disease.⁴
• Prognosis:
  • Untreated patients have a high mortality.
  • Immunocompromised patients with bacillary angiomatosis or peliosis hepatitis respond well to antibiotics.
  • Relapses are common.

Synonym: Carrion disease

• Epidemiology:
  • B. bacilliformis is common in the Peruvian Andes and transmission is limited to elevations of 1000-3000 meters because of the habitat of the sand fly vector.
• Presentation:
  • Bacteraemia of Oroya fever begins 3-12 weeks after a sand fly bite.
  • May be mild where endemic (Andean Peru, Ecuador, Colombia, Chile, Bolivia, and Guatemala) but may be severe in newly infected patients, with profound haemolytic anemia, which is often fatal if untreated.
  • Severe illness causes fever, headache, dyspnoea, mental state changes, and seizures.
  • Weeks or months later, untreated survivors develop verruga peruana lesions (angiomatous skin lesions), which begin as small nodules and then grow. They then form vascular lesions, which ulcerate, bleed, and then heal by fibrosis over several months.
• Differential Diagnosis:
  • Other serious causes of fever in a patient who has returned from a developing country include dengue fever, malaria, tuberculosis and babesiosis.
• Investigations:
  • Haemolytic anaemia, thrombocytopenia and abnormal liver function tests.
  • Serology testing is the most cost-effective method to confirm the diagnosis.
• Management:
  • Both chloramphenicol or doxycycline are effective and need to be given for at least one week. Chloramphenicol is usually reserved for severe cases.⁴
• Prognosis:
  • Untreated patients have a 95% mortality rate.
  • Persistent bacteraemia may occur in survivors.

• B. elizabethae is a rare cause of endocarditis.
• B. washoensis is associated with cardiac disease (ground squirrel host).
• B. vinsonii (subspecies arupensis) causes fever and neurological symptoms.
• B. grahamii associated with neuroretinitis, as is B. henselae.