Bartonella spp. are Gram-negative bacteria and are facultative intracellular parasites. 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 Bartonella are associated with an increasing range of diseases.² The range of infection varies from mild lymphadenopathy seen in cat scratch disease, to life-threatening systemic disease in immunocompromised patients.

Bartonella infections

Bartonella spp. have been isolated from a variety of mammalian species, most often rodents, ruminants and carnivores. Transmission is generally considered to be by arthropod vectors. Infections caused by Bartonella spp. include:^3,4

• Cat-scratch disease: B. henselae.
• Trench fever: B. quintana.
• Bacillary angiomatosis: B. henselae and B. quintana.
• Oroya fever and verruga peruana: B. bacilliformis.

Cat scratch disease

See separate Cat Scratch Disease article.

Trench fever⁵

Synonyms: shinbone fever, 5-day fever, Wolhynia fever, quintana fever, His-Werner disease

• Epidemiology:
  • It is caused by B. 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, bone and muscle pain, headache, dizziness, and pain behind the eyes. Some patients have diffuse symptoms without fever.
  • It 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. cytomegalovirus (CMV), HIV seroconversion.
  • Other causes of culture-negative endocarditis include legionellosis, Q Fever and slow-growing streptococci.
• Complications:
  • Persistent bacteraemia with B. henselae may develop in people with AIDS.
• Prognosis:
  • Usually self-limiting. Trench fever reinfection may occur within 3-6 months because antibodies do not give full protection.

Bacillary angiomatosis and peliosis hepatis

• Both B. henselae and B. quintana may cause bacillary angiomatosis, which most often occurs in HIV-positive patients.¹ Patients should therefore have HIV antibodies and CD4 lymphocyte counts checked.
• Bacillary angiomatosis is characterised by the proliferation of blood vessels, resulting in them forming tumour-like masses in the skin and other organs.
• Bacillary angiomatosis is often associated with peliosis hepatis, which is characterised by multiple blood-filled cavities throughout the liver. Peliosis occasionally affects other parts of the body, e.g. the spleen.
• Presentation:
  • Symptoms depend on the anatomical site involved and may include fever, tender lymphadenopathy, and skin lesions.
  • Lesions are often dark purple and resemble Kaposi's sarcoma.
  • There may be enlargement of the liver, lymph nodes or spleen.
  • Endocarditis is sometimes associated with Bartonella spp. infection (including B. henselae, B. quintana, B. elizabethae).
  • Homelessness and alcoholism are risk factors for B. quintana 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 has been reported.
  • FBC usually demonstrates anaemia and LFTs show elevated serum alkaline phosphatase.
• Prognosis:
  • Untreated patients have a high mortality.
  • Immunocompromised patients with bacillary angiomatosis or peliosis hepatis respond well to antibiotics.
  • Relapses are common.

Oroya fever and verruga peruana

Synonyms: Carrión's disease (Oroya fever); Peruvian wart (verruga peruana)

Oroya fever occurs in the acute phase of infection and the lesions of verruga peruana occur in the chronic delayed stage of infection.

• Epidemiology:
  • B. bacilliformis is common in the Peruvian Andes and transmission is limited to elevations of 1,000-3,000 m because of the habitat of the sand fly vector.
• Presentation:
  • Bacteraemia in 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 anaemia, 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 nodules), which begin as small nodules and then grow. They then form vascular lesions, which ulcerate, bleed, and then heal by fibrosis over several months.
  • Routine blood tests show haemolytic anaemia, thrombocytopenia and abnormal LFTs.
• Differential diagnosis:
  • Other serious causes of fever in a patient who has returned from a developing country include dengue fever, malaria, tuberculosis and babesiosis.
• Prognosis:
  • The mortality and morbidity of acute infection is variable and the mortality associated with verruga peruana is very low.¹
  • Persistent bacteraemia may occur in survivors.

Investigations¹

• Microscopic examination of Giemsa-stained blood smears is used to detect B. bacilliformis in patients who may have Oroya fever.
• Other Bartonella species are visible only with silver stains, if they stain at all, and these stains are not specific.
• Cultures:
  • Cultures, particularly blood cultures, are often unhelpful for the diagnosis of Bartonella spp. infection.⁵
  • Cultures may be useful in patients who have other manifestations of either B. henselae or B. quintana infection, including fever of unknown origin, neuroretinitis, encephalitis, culture-negative endocarditis, and peliosis or bacillary angiomatosis. Fresh media are required to increase the chance of isolation.
  • Antibiotic susceptibility is not routinely tested in patients with bartonellosis because susceptibility studies may fail to predict response to therapy.
• Serology:
  • Serology testing is the most cost-effective method to confirm the diagnosis in most patients with bartonellosis but there may be cross-reactivity with other bacteria (e.g. other bartonellae, Chlamydia spp., Coxiella spp.) and serology testing may be unhelpful with immunocompromised patients.
  • Some patients never develop detectable antibodies. However, the serology results of some patients remain positive long after exposure and recovery from their illness.
• Polymerase chain reaction (PCR):
  • PCR genome testing is sensitive and specific but difficult to perform.
  • PCR has played an important role in the diagnosis of Bartonella endocarditis. In cases of suspected Bartonella endocarditis, PCR on cardiac valve tissue is very sensitive and is not affected by antibiotic treatment prior to surgery.
  • Because of the cross-reactivity between Bartonella spp. and other bacteria, PCR analysis of tissue and body fluid is the most specific test, especially in identifying distinct genotypes.
• Imaging:
  • CT scanning of the chest and abdomen may reveal mediastinal, retroperitoneal, or mesenteric lymph node enlargement.
  • In patients with bacillary angiomatosis/peliosis, CT scanning or MRI of the involved organ shows the enhancing lesions (e.g. brain, liver). Radiography of the bone may show osteolytic lesions and bone destruction.

Management

Trench fever

• Doxycycline is given for at least four weeks and a longer course is recommended for immunocompromised patients and when the liver or other organs are involved. Chloramphenicol may be used in severe cases.⁶
• Bartonella endocarditis: the recommended treatment is doxycycline for 6 weeks, with gentamicin for 2 weeks.⁶ Surgical resection of heart valves is usually required. Mortality rate of Bartonella endocarditis is 30%.

Bacillary angiomatosis and peliosis hepatis

• Effective antibiotics include erythromycin, doxycycline, azithromycin, clarithromycin, or a fluoroquinolone.
• Doxycycline combined with rifampin is effective for patients with severe disease but treatment is often required for three months or longer.⁶

Oroya fever and verruga peruana

• Either chloramphenicol or doxycycline is effective and needs to be given for at least one week. Chloramphenicol is usually reserved for severe cases.⁶

Document references

1. Hammoud KA et al; Bartonellosis, eMedicine, Dec 2010
2. Maguina C, Guerra H, Ventosilla P; Bartonellosis. Clin Dermatol. 2009 May-Jun;27(3):271-80. [abstract]
3. Biswas S, Rolain JM; Bartonella infection: treatment and drug resistance. Future Microbiol. 2010 Nov;5:1719-31. [abstract]
4. Adamska M; (Bartonella spp. as a zoonotic pathogens transmitting by blood-feeding Wiad Parazytol. 2010;56(1):1-9. [abstract]
5. Lea AS; Trench Fever, eMedicine, Feb 2009
6. Rolain JM et al; Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother. 2004 Jun;48(6):1921-33

Acknowledgements