Bartonella henselae is a Gram-negative bacterium belonging to the genus Bartonella, a group of bacteria that can infect humans and animals worldwide.
It is the primary causative agent of cat-scratch disease (CSD), a zoonotic infection associated mainly with domestic and wild cats.
Humans can acquire B. henselae through cat scratches or bites, as well as through exposure to flea vectors associated with cats.
Infection is often mild and self-limiting, particularly in otherwise healthy individuals.
Many healthy individuals remain asymptomatic after infection, while those who develop mild disease typically recover without specific treatment.
Although most infections are uncomplicated, B. henselae can occasionally cause more serious or systemic disease, particularly in immunocompromised individuals.
Taxonomy and Classification of Bartonella henselae
Domain: Bacteria
Kingdom: Pseudomonadati
Phylum: Pseudomonadota
Class: Alphaproteobacteria
Order: Hyphomicrobiales
Family: Bartonellaceae
Genus:Bartonella
Species: Bartonella henselae
Morphology and Microscopy of Bartonella henselae
Bartonella henselae is a small, fastidious, Gram-negative bacterium with a pleomorphic morphology.
It typically appears as short or slightly curved bacillary (rod-shaped) cells.
The cells measure approximately 0.3–0.6 µm in diameter and 1.0–1.7 µm in length.
B. henselae is non-motile, non-spore-forming, and non-capsulated.
It is a facultative intracellular bacterium, allowing it to survive and replicate within host cells.
Following Gram staining, the organism appears as faintly pink, short, or slightly curved rods when examined microscopically.
Cultural and Growth Characteristics of Bartonella henselae
Bartonella henselae is an aerobic and capnophilic bacterium that grows optimally in an atmosphere containing approximately 5–10% CO₂.
Optimum temperature: 35–37°C
Optimum pH: 7.2–7.4
The organism is fastidious and requires enriched culture conditions for growth.
Growth on Culture Media
MacConkey Agar: No growth is observed.
Blood Agar with 5% sheep blood: No growth is observed under routine conditions.
Biphasic Medium (BM):
Broth phase: Abundant growth produces dense, granular turbidity without pigmentation.
Solid phase: Colonies are approximately 1–3 mm in diameter, circular, elevated, smooth-surfaced, and have an entire margin. They appear whitish to translucent.
Tryptic Soy Broth (TSB): Abundant growth with dense, granular turbidity and no pigmentation.
Tryptic Soy Agar (TSA) with 5% sheep blood: Colonies are approximately 1–3 mm, circular, smooth, viscid, low-convex, and iridescent, with an entire margin. They are non-hemolytic, sticky, not embedded in the medium, and immiscible.
Brain Heart Infusion Agar (BHIA) with 5% sheep blood: Colonies are approximately 1–3 mm, low-convex, smooth, viscid, and iridescent, with an entire margin. They are non-hemolytic, sticky, not embedded in the medium, and immiscible.
Biochemical and Identification Tests of Bartonella henselae
Gram staining: Gram-negative
Catalase: Negative or weakly positive
Oxidase: Negative
Urease: Negative
Nitrate reduction: Negative
Indole: Negative
Carbohydrate fermentation: Non-fermentative
Identification: Conventional biochemical tests have limited utility because B. henselae is fastidious and slow-growing; PCR and sequencing may be used for more definitive identification.
Pathogenesis of Bartonella henselae
Entry into the Host
B. henselae enters the body through breaks in the skin, typically following scratches or bites from infected cats.
Local Infection
After entering the skin, the bacteria multiply locally, producing a primary papule or pustule at the site of inoculation.
The bacteria can subsequently invade endothelial cells and macrophages.
Lymphatic Spread
The bacteria spread through the lymphatic system to the regional lymph nodes.
This results in lymphadenitis, the characteristic feature of cat-scratch disease.
Affected lymph nodes become enlarged and tender and may occasionally undergo suppuration.
Intracellular Survival
B. henselae can survive within macrophages, helping it evade immune-mediated destruction.
Infection of endothelial cells can also induce cellular and vascular changes that support bacterial persistence.
Vascular Proliferation
The bacterium can stimulate angiogenesis, or the formation of new blood vessels.
This vascular proliferation can lead to bacillary angiomatosis, particularly in immunocompromised individuals.
The process involves bacterial stimulation of host-cell growth and angiogenic signaling pathways.
Systemic Dissemination
In some infections, B. henselae can disseminate through the bloodstream and reach organs such as the liver, spleen, and eyes.
Systemic infection may result in hepatic lesions and neuroretinitis.
Severe or disseminated disease is more likely in immunocompromised individuals, including people with advanced HIV infection.
Virulence Factors of Bartonella henselae
Lipopolysaccharide (LPS)
Contributes to immune evasion.
Helps the bacterium avoid triggering a strong host immune response.
Trimeric Autotransporter Adhesins (BadA and Vomps)
Promote bacterial autoaggregation.
Facilitate attachment to the extracellular matrix and host cells.
Contribute to host-cell binding through β1-integrins.
Promote activation of HIF-1 and NF-κB signaling pathways.
Help inhibit phagocytosis by macrophages, supporting bacterial persistence.
VirB/D4 Type IV Secretion System (T4SS)
Delivers bacterial effector proteins into host cells.
Contributes to inhibition of apoptosis.
Promotes proinflammatory signaling.
Is important for invasome formation, facilitating bacterial internalization.
Contributes to the modulation of angiogenesis.
Outer Membrane Proteins (OMPs)
Promote adhesion to host cells.
Contribute to activation of NF-κB signaling.
Deformin
Induces the formation of invaginations in erythrocyte membranes.
Facilitates interactions between B. henselae and red blood cells.
Hemin-Binding Proteins
Facilitate hemin acquisition and binding.
Also contribute to fibronectin binding, supporting bacterial adhesion.
OMP43
Contributes to fibronectin binding.
Facilitates attachment to host cells.
Trw Type IV Secretion System
Plays an important role in adhesion to the surface of erythrocytes.
Supports the ability of B. henselae to establish persistent infection within red blood cells.
Surface Proteins
Contribute to host-cell adhesion.
Promote cellular signaling through interaction with β1-integrins.
Epidemiology and Transmission of Bartonella henselae
Bartonella henselae is the primary causative agent of cat-scratch disease (CSD), a usually mild zoonotic infection that occurs worldwide.
CSD can affect people of all ages, but children are particularly susceptible because of their greater likelihood of contact with cats and kittens.
In the United States, approximately 24,000 people are affected by CSD each year.
Approximately 4.5–9.4 cases per 100,000 people are reported annually.
Around 55% of reported CSD cases occur in individuals younger than 18 years, with approximately 60% of these pediatric cases occurring in boys.
Children aged 5–9 years have a particularly high incidence, likely because of increased exposure to kittens.
CSD shows seasonal variation in the United States, with more than half of cases occurring between September and January.
Severe manifestations can occur in young children and adult women and may require hospitalization.
During the COVID-19 pandemic, increased CSD incidence was reported in some areas, possibly because quarantine and stay-at-home measures increased close contact between people and domestic cats.
A meta-analysis estimated a global B. henselae prevalence of approximately 15.3%.
Seroprevalence among cats varies geographically. For example, approximately 16% of pet cats in Central Italy and 39% of stray cats in Northern Italy have been reported to be seropositive.
The prevalence of B. henselae among cats in Croatia and neighboring regions of Central and Southeastern Europe remains uncertain because of limited epidemiological data.
Reservoir and Vector
Domestic cats, particularly kittens younger than 1 year, are the major reservoirs of B. henselae.
Cats acquire the bacterium primarily through the cat flea (Ctenocephalides felis), which facilitates transmission between cats.
Infected cats can develop bacteremia and carry the bacterium in their bloodstream for months without apparent illness.
Fleas play an important role in cat-to-cat transmission, whereas their direct transmission of B. henselae to humans appears to be uncommon.
Ticks and other arthropods have been proposed as potential vectors, but their role in transmission to humans has not been definitively established.
Routes of Transmission
Cat Scratches or Bites
This is the most common route of transmission to humans.
Bacteria can enter through broken skin following a scratch or bite from an infected cat.
Scratches contaminated with infected flea feces may increase the risk of transmission.
Contact with Cat Saliva or Blood
Transmission may occasionally occur when infected cat saliva or blood comes into contact with an open wound or damaged skin.
This route is considered less common than scratches or bites.
Arthropod Vectors
Cat fleas (C. felis) are important for maintaining and transmitting B. henselae among cats.
Their role in direct transmission to humans is considered limited.
Ticks and other arthropods are potential vectors, but definitive evidence for human transmission remains limited.
Person-to-Person Transmission
Direct human-to-human transmission is extremely rare and is not considered a major route of spread.
Risk Factor
Close contact with cats or kittens
Individuals who live with or frequently interact with cats or kittens have an increased risk of exposure to B. henselae.
The risk is particularly increased following cat scratches or bites.
HIV Infection
People living with HIV, particularly those with significant immune suppression, are at increased risk of B. henselae-associated disease.
Immunocompromised Status
Individuals with weakened immune systems are at greater risk of severe or disseminated infection and complications.
The incubation period is typically 3–10 days following a cat scratch or bite.
Common clinical features include:
Papule or pustule at the site of inoculation
Regional lymphadenopathy
Mild fever
Fatigue
Malaise
In otherwise healthy individuals, symptoms are generally self-limiting and usually resolve within 2–4 weeks.
Bacillary Angiomatosis
Occurs primarily in immunocompromised individuals, particularly those with advanced HIV infection.
Characteristic manifestations include:
Red, raised, vascular skin lesions, which may appear as papules or nodules
Bleeding from the lesions
Fever
Malaise
Muscle, bone, or joint pain
Loss of appetite
The infection may involve internal organs, including the liver, spleen, and bone.
Bacillary Peliosis Hepatis
Characterized by blood-filled vascular lesions, particularly in the liver and sometimes the spleen.
May cause:
Hepatosplenomegaly
Abdominal pain
Anemia
Ocular Manifestations
B. henselae infection can cause neuroretinitis, involving inflammation of the retina and optic nerve.
Common symptoms include:
Blurred vision
Visual-field defects
Neurological and Cardiovascular Complications
Severe or disseminated infection may occasionally lead to:
Encephalopathy
Endocarditis
Heart failure
Parinaud Oculoglandular Syndrome
B. henselae can cause Parinaud oculoglandular syndrome, an ocular manifestation associated with conjunctival inflammation and regional lymphadenopathy.
Laboratory Diagnosis of Bartonella henselae
Sample Collection
The appropriate clinical specimen depends on the type of infection:
Febrile patients: Blood
Cat-scratch disease (CSD): Lymph-node aspirate
Bacillary angiomatosis or peliosis: Biopsy of skin or affected lesions
Neuroretinitis: Ocular fluid
Gram Staining
B. henselae appears as faintly pink, short or slightly curved Gram-negative rods.
Warthin–Starry silver staining may demonstrate black-staining bacilli in tissue sections.
Giemsa staining can demonstrate intracellular bacteria within endothelial cells or macrophages.
Culture
B. henselae is a fastidious, slow-growing organism, so specialized culture conditions are required.
MacConkey Agar: No growth
Blood Agar with 5% sheep blood: No growth
Biphasic Medium (BM):
Broth: Abundant growth with dense, granular turbidity and no pigmentation.
Solid phase: Colonies are approximately 1–3 mm, circular, elevated, smooth-surfaced, and have an entire margin; colonies are whitish to translucent.
Tryptic Soy Broth (TSB): Abundant growth with dense, granular turbidity and no pigmentation.
Tryptic Soy Agar (TSA) with 5% sheep blood: Colonies are approximately 1–3 mm, circular, smooth, viscid, low-convex, and iridescent, with an entire margin. They are non-hemolytic, sticky, not embedded in the medium, and immiscible.
Brain Heart Infusion Agar (BHIA) with 5% sheep blood: Colonies are approximately 1–3 mm, low-convex, smooth, viscid, and iridescent, with an entire margin. They are non-hemolytic, sticky, not embedded in the medium, and immiscible.
Biochemical Tests
Conventional biochemical testing has limited diagnostic value because B. henselae is fastidious and slow-growing.
Characteristic results include:
Gram staining: Negative
Catalase: Negative or weakly positive
Oxidase: Negative
Urease: Negative
Nitrate reduction: Negative
Indole: Negative
Carbohydrate fermentation: Non-fermentative
Serology
Serological testing detects IgG and IgM antibodies against B. henselae.
Common methods include:
Indirect fluorescent antibody (IFA) testing
Enzyme-linked immunosorbent assay (ELISA)
Serology is useful for supporting the diagnosis of cat-scratch disease and for retrospective diagnosis.
Cross-reactivity with other Bartonella species can occur, which may limit specificity.
Molecular Tests
Polymerase chain reaction (PCR) detects B. henselae DNA in specimens such as blood, tissue, or lesion aspirates.
PCR assays may target genes including 16S rRNA and gltA (citrate synthase).
Molecular testing provides species-level identification and is particularly useful when culture is difficult or when rapid confirmation is required.
PCR can be especially valuable in early infection and immunocompromised patients.
Histopathology
Lymph-node biopsy may demonstrate granulomatous inflammation in cat-scratch disease.
Bacillary angiomatosis is characterized by vascular proliferation and associated inflammatory changes in affected tissue.
Treatment of Bartonella henselae Infection
Mild Infection
Cat-scratch disease in otherwise healthy individuals is often self-limiting, with symptoms generally resolving within 2–8 weeks.
Management may primarily involve supportive care, including:
Analgesics, such as paracetamol, for pain and fever.
Warm compresses to help relieve discomfort associated with enlarged lymph nodes.
Azithromycin may be used in selected cases and can shorten the duration of lymph-node enlargement.
Moderate Infection
Depending on the clinical presentation, antimicrobial therapy may include:
Azithromycin
Doxycycline
Rifampin
Ciprofloxacin
Lymph-node aspiration may be considered when lymph nodes are severely painful or become suppurative.
Severe or Disseminated Infection
More extensive disease generally requires prolonged antimicrobial therapy.
Doxycycline combined with rifampin may be used for severe or disseminated infections.
Alternative agents may include:
Erythromycin
Clarithromycin
Ciprofloxacin
Trimethoprim–sulfamethoxazole
Treatment duration may range from several weeks to several months, depending on the site and severity of infection.
Serious Complications
Severe manifestations such as Bartonella-associated endocarditis may require prolonged antimicrobial treatment.
Doxycycline with gentamicin may be used in selected serious infections under specialist management.
In severe cases of infective endocarditis with significant valvular damage, surgical valve replacement may be required.
Prevention and Control of Bartonella henselae
Practice hand hygiene: Wash your hands thoroughly with soap and water after handling, touching, or playing with cats and kittens.
Control fleas: Keep cats indoors when possible to reduce exposure to fleas and consult a veterinarian about appropriate flea-control measures.
Avoid stray cats: Avoid unnecessary contact with stray or unfamiliar cats and kittens, particularly animals that may have fleas.
Choose cats carefully: Individuals with a weakened immune system should consider adopting an adult cat (≥1 year old) rather than a kitten, as kittens are more commonly associated with B. henselae transmission.
Clean and protect wounds: Promptly clean and cover scratches, bites, and other skin breaks. Do not allow cats to lick open wounds or damaged skin.
Prevent scratches and bites: Handle cats gently and avoid rough play that may result in scratching or biting.
Maintain general hygiene: Regular handwashing and routine personal hygiene can help reduce exposure to infectious material.
Protective clothing: When working in environments with potential exposure to cats, fleas, or other vectors, wear appropriate clothing that provides adequate skin coverage.
Avoid sharing personal items: Do not share towels, bedding, clothing, or other personal items when there is a risk of exposure to body fluids or contaminated material.
Conclusion
Bartonella henselae is a Gram-negative, fastidious, facultative intracellular bacterium and the primary causative agent of cat-scratch disease (CSD).
Human infection occurs mainly through cat scratches, bites, or exposure to infected cat fleas.
In most immunocompetent individuals, infection is mild and self-limiting, with spontaneous recovery in many cases.
However, immunocompromised individuals are at increased risk of severe or disseminated disease, including bacillary angiomatosis, bacillary peliosis hepatis, encephalopathy, and endocarditis.
Laboratory diagnosis may involve culture, serological testing, histopathology, and molecular methods such as PCR, depending on the clinical presentation and specimen available.
No licensed vaccine is currently available for prevention of human B. henselae infection.
Prevention therefore relies primarily on responsible cat handling, prompt care of scratches and bites, effective flea control, and good personal hygiene.
Early recognition of infection, appropriate laboratory confirmation, and timely management are particularly important in high-risk and immunocompromised individuals.
References
Anderson, B. E., Goldsmith, C. S., Johnson, A., Padmalayam, I., & Baumstark, B. R. (2004). Growth characteristics of Bartonella henselae in a novel liquid medium: Primary isolation, growth-phase-dependent phage induction, and metabolic studies. Journal of Clinical Microbiology, 42(2), 614–621. https://pubmed.ncbi.nlm.nih.gov/14766538/
Diddi, K., Chaudhry, R., Sharma, N., & Dhawan, B. (2013). Strategy for identification & characterization of Bartonella henselae with conventional & molecular methods. Indian Journal of Medical Research, 137(2), 380–387.
Harms, A., & Dehio, C. (2012). Intruders below the radar: Molecular pathogenesis of Bartonella spp. Clinical Microbiology Reviews, 25(1), 42–78. https://doi.org/10.1128/CMR.05009-11
Sabir, S., Daley, S. F., & Huang, B. (2026). Cat scratch disease. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK482139/
Tay, S. Y., Freeman, K., & Baird, R. (2021). Clinical manifestations associated with Bartonella henselae infection in a tropical region. The American Journal of Tropical Medicine and Hygiene, 104(1), 198–206. https://doi.org/10.4269/ajtmh.20-0088
University of Alabama at Birmingham, Children's of Alabama. (n.d.). Bug du jour: Bartonella (Antimicrobial Stewardship Program). https://www.childrensal.org/sites/default/files/workfiles/antimicrobial/Bug_du_Jour-Bartonella.pdf
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