Bartonella: From the Andes to the Cat Scratch

It was an early Saturday morning, around 7:00 a.m., when my pager went off with a message: “The Bartonella titers are very positive!”

I was on coverage and had no idea what the team was referring to. Before calling them back, I reviewed the chart to confirm that the results were consistent with the clinical picture. They were more than consistent—they were remarkable. The patient had presented with general malaise and a lower extremity rash, was found to have acute renal failure with biopsy showing crescentic glomerulonephritis, and also had a positive c-ANCA. Initially treated for possible small vessel vasculitis with steroids, the patient’s exposure to multiple cats (and kittens) had prompted Bartonella serologies to be sent.

I called the team back and said, with some excitement:
“This patient most likely has small vessel vasculitis with glomerulonephritis secondary to Bartonella henselae, and most likely endocarditis!”

That excitement is why I decided to write about Bartonella spp. today.

We’ll focus on the three most clinically relevant Bartonella species in human disease, while acknowledging that others have been implicated but are beyond the scope of this post. Let’s go in chronological order.

Bartonella bacilliformis: Where the Name Came From

Although Bartonella species have likely been infecting humans for at least 4,000 years (the oldest DNA evidence comes from Bartonella quintana found in a 4,000-year-old human tooth), the story of B. bacilliformis begins in Peru.

In 1905, Peruvian physician Alberto Leonardo Barton Thompson observed intraerythrocytic organisms in patients suffering from anemia and fever in the region of Oroya, after railroad workers had developed similar symptoms in 1875. This led to the naming of the genus Bartonella in 1913.

Even earlier, in 1885, a medical student named Daniel Carrión attempted to prove the link between the acute febrile illness (“Oroya fever”) and the chronic nodular lesions known as Verruga peruana. He inoculated himself with material from the verrucous lesions and tragically died of Oroya fever. The entire disease spectrum is now known as Carrión’s disease in his honor.

Today, B. bacilliformis is mainly confined to the Andes of Peru, Ecuador, and Colombia, between 500–3200 m altitude—restricted by its sand fly vector (Lutzomyia, the same vector for Leishmania spp. in the new world).

Clinical Phases

• Oroya fever (acute phase): Occurs 3–12 weeks after inoculation. Presents with high fever, chills, sweats, headache, profound anemia (from erythrocyte invasion and destruction), myalgias, jaundice, lymphadenopathy, and complications such as delirium, seizures, or hepatic dysfunction.

• Verruga peruana (chronic phase): Characterized by nodular, angiomatous skin lesions, which may appear weeks to months after the acute illness.

Diagnosis

In endemic regions, diagnosis is based on exposure, clinical syndrome, and visualization of bacilli in erythrocytes on Giemsa-stained blood smears—reminiscent of malaria. Molecular testing and serologic is available but limited in this areas.

Treatment

Evidence is limited and mostly based on case series.

• Oroya fever: Ciprofloxacin + ceftriaxone for 14 days (alternatives: chloramphenicol + β-lactam).

• Verruga peruana: Azithromycin for 7–14 days (alternatives: rifampin for 21–28 days or ciprofloxacin for 14 days).
  Note: Rifampin monotherapy is only recommended for verruga peruana, not for other Bartonella infections.

Bartonella quintana: The WWI Foe

Previously called Rochalimaea quintana, this species was responsible for trench fever in World War I. The name “quintana” comes from its characteristic five-day relapsing fevers (quintan fever).

Its only known vector is the human body louse (Pediculus humanus), and humans are its sole reservoir. It re-emerged in the 1980s–1990s in urban homeless populations and in people with AIDS.

Clinical Spectrum

• Trench fever (self-limited relapsing fevers)

• Chronic bacteremia

• Endocarditis (often without prior valvular disease)

Treatment

• Isolated bacteremia (immunocompetent, endocarditis ruled out): Doxycycline for 4 weeks + gentamicin for the first 2 weeks.

• Endocarditis: See below (same as B. henselae).

Bartonella henselae: The One I Think About When My Cat Scratches Me

Discovered in the 1980s, B. henselae is best known for Cat Scratch Disease (CSD). Bartonella henselae, the species I think about every time my cat scratches me, is primarily transmitted from cats, especially kittens, to humans. Cats often carry the bacterium in their red blood cells without showing any symptoms, while fleas feeding on these cats pick up the bacteria and deposit it in their feces. Humans typically become infected when scratched or bitten by a cat whose claws are contaminated with flea feces, or through direct contact with flea dirt on the cat’s fur. Even healthy-appearing kittens can harbor the bacterium, which is why a seemingly innocent scratch can sometimes lead to infection.

Immunocompetent Hosts

• Classic CSD: Papule at inoculation site with ipsilateral lymphadenopathy (head, neck, upper extremity). Usually self-limited.

• Atypical CSD: Can involve hepatitis, pneumonitis, encephalitis, or ocular disease.

  • Parinaud oculoglandular syndrome: granulomatous conjunctivitis with preauricular lymphadenitis. (Not to confuse with Parinaud’s syndrome, describe by the same french physician Henri Parinaud)

  • Neuroretinitis: unilateral vision loss with “macular star” exudates.

Immunocompromised Hosts

Two syndromes are particularly important in immunocompromised patients (HIV with low CD4 counts, SOT, BMT, or patients on immunosuppression):

Bacillary Angiomatosis (BA)

• A vascular proliferative disease first described in patients with advanced HIV infection.

• Skin lesions can mimic Kaposi sarcoma or pyogenic granulomas, and appear as red-to-purple papules, nodules, or subcutaneous masses. They may ulcerate and can occur in clusters or diffusely.

• Pathologically, BA is characterized by lobular proliferation of small blood vessels with plump endothelial cells and mixed inflammatory infiltrates. Warthin-Starry stain highlights clumps of bacilli.

• Lesions can also involve lymph nodes and bone (osteomyelitis).

• Clinically important because it responds dramatically to antibiotics (unlike Kaposi sarcoma).

Hepatic and Splenic Peliosis (BP)

• A striking visceral counterpart to BA, characterized by blood-filled cystic spaces in the liver or spleen.

• Presents with fever, hepatosplenomegaly, abdominal pain, anemia, and elevated alkaline phosphatase. Cytopenias are common.

• Imaging (US or CT) reveals multiple hypodense lesions, often mistaken for abscesses or malignancy.

• Histology shows numerous blood-filled cavities without endothelial lining (true peliosis), often with Bartonella bacilli demonstrable on Warthin-Starry stain.

• B. henselae is the main culprit; B. quintana less commonly.

Both BA and BP highlight Bartonella’s angiotropic properties—stimulating endothelial proliferation and vascular remodeling in immunocompromised settings.

Treatment of BA and BP

• First-line: doxycycline (100 mg PO/IV every 12 h) for 3–6 months.

• Severe cases: add rifampin (300 mg PO/IV every 12 h), though interactions with ART and immunosuppressants must be considered.

• Alternatives: azithromycin (500 mg daily) or clarithromycin (500 mg BID).

• Relapse is common, especially with ongoing immunosuppression, so prolonged or suppressive therapy (chronic doxycycline) is sometimes needed.

Endocarditis

Both B. henselae and B. quintana are now recognized as important causes of culture-negative endocarditis. In fact, Bartonella species may account for up to 3–5% of all blood culture–negative cases.

There are some patterns: B. quintana is more often associated with endocarditis in people without prior valvular disease (often homeless or louse-exposed populations), while B. henselae tends to affect individuals with preexisting valvular abnormalities. However, this distinction may partly reflect selection bias.

Importantly, Bartonella endocarditis is frequently associated with glomerulonephritis and vasculitic features. Biopsies often show crescentic GN with immune complex deposition. C3 codominant (80%) with strong IgM (65%) and/or C1q (55%), or pauci-immune (10%), with predominantly mesangial deposits and limited exudative features. Strongly recommend this article (PMID: 40303199). Up to 80% of patients can be c-ANCA positive—leading to frequent misdiagnosis and immunosuppressive therapy.

Diagnosis usually relies on serology (very high IgG titers, often >1:1024) and PCR on excised valve tissue. Cross-reactivity with Coxiella burnetii and Chlamydia spp. is common, so results must be interpreted carefully.

Treatment

• Cat Scratch Disease: Azithromycin (shortens lymphadenopathy).

• Endocarditis: Doxycycline + rifampin for 6 weeks (gentamicin may be avoided in renal dysfunction).

• Bacillary angiomatosis / peliosis: Doxycycline or macrolides for 3–6 months; rifampin can be added in severe cases.

Musical Coda