Bartonella species are vector-borne, Gram-negative bacteria that invade red blood cells and the cells lining blood vessels. More than 45 species have been described, but three dominate human disease: B. henselae, the agent of cat scratch disease, transmitted chiefly by cat fleas and scratches from infected cats; B. quintana, the agent of trench fever, spread by the human body louse; and B. bacilliformis, restricted largely to South America. In immunocompetent people, cat scratch disease typically resolves on its own within two to four months, presenting as swollen lymph nodes, skin lesions, fatigue, and headache. In contrast, B. quintana infection spans a broad clinical spectrum, from recurrent fever with severe leg pain to chronic bacteremia, culture-negative infective endocarditis, bacillary angiomatosis, and bacillary peliosis, conditions that emerge mainly when the immune system cannot contain the organism.

That distinction matters because the host immune response is the central determinant of how Bartonella infection unfolds. In people with intact immunity, the pathological response is typically granulomatous and suppurative, effectively walling off the bacteria. In immunocompromised individuals, including organ transplant recipients and people with HIV, the same organisms can drive proliferative vascular lesions that grow rapidly. Patients with CD4 T-cell counts below 50 cells per microliter are considered especially vulnerable to severe disease and chronic opportunistic infection. Iran has already seen warning signs: the first molecularly confirmed case of B. quintana bacillary angiomatosis in an HIV-infected patient was reported there in 2021, and more than eight Bartonella species have since been identified in insects and livestock reservoirs across the country, five of them known to cause human disease.

To quantify the scale of exposure, the research team enrolled 200 participants between September 2023 and May 2024: 150 patients with HIV infection recruited from the Infectious Diseases Department and HIV clinic at Imam Khomeini Hospital, a referral university hospital in Tehran, and 50 randomly selected healthy controls. Within the HIV-positive group, 39 individuals met the criteria for AIDS, defined by CD4 counts below 200 cells per microliter or clinical AIDS-defining conditions, while 111 had higher counts. Each participant provided five milliliters of venous blood after informed consent, completed a structured questionnaire covering demographics, animal contact, tick and flea exposure, social status, and transfusion history, and had serum separated and stored at minus 20 degrees Celsius under cold chain conditions at the Pasteur Institute.

The serological workhorse of the study was the indirect immunofluorescence assay, or IFA, the technique recommended by the US Centers for Disease Control and Prevention for detecting antibodies against B. henselae and B. quintana. Because the samples came from HIV-positive individuals, all sera were first treated with Triton X-100 for 30 minutes at 37 degrees Celsius to reduce biocontamination risk, a pretreatment shown to inactivate HIV particles without compromising antibody detection. For IgG testing, sera were serially diluted from 1:64 up to 1:2048 and applied to slides coated with fixed bacterial antigens; after incubation and washing, a fluorescein-labeled anti-human IgG conjugate was added, and fluorescence was read at 400-fold magnification. The highest dilution showing distinct apple-green fluorescence defined the endpoint titer, with 1:64 or above scored as positive. IgM testing followed a parallel protocol on a randomly selected subset of 48 participants, using IgG sorbent to strip competing IgG antibodies before dilution, with titers of 1:24 or above considered positive.

The results revealed substantial background exposure. Across all 200 participants, IgG seroprevalence was 24.0 percent for B. henselae and 22.0 percent for B. quintana, while IgM seroprevalence in the tested subset reached 18.8 percent and 22.9 percent respectively. Strikingly, the healthy controls fared no better: B. henselae IgG was found in 30.0 percent of controls and 30.0 percent of AIDS patients, versus 18.3 percent of HIV-positive patients without AIDS, and B. quintana IgG appeared in 26.0 percent of controls, 28.3 percent of AIDS patients, and 17.3 percent of the HIV-positive group. None of these between-group differences reached statistical significance, suggesting that Bartonella circulation in this region extends well beyond the immunocompromised clinic population.

Risk factor analysis sharpened the picture. In multivariable logistic regression, higher age emerged as protective against B. quintana IgG seropositivity, with an odds ratio of 0.48, while a history of drug use nearly tripled the odds, at 3.28. For B. henselae, every body mass index category above underweight carried significantly lower odds of IgG positivity compared with a BMI below 18.5, with odds ratios falling as low as 0.16, and drug use again raised the odds, at 2.46. Underlying chronic diseases were associated with reduced seropositivity, an odds ratio of 0.31, a counterintuitive finding the authors interpret cautiously. Notably, contact with cats, dogs, or other animals, often assumed to be the main route of exposure, showed no significant association with seropositivity for either species, nor did homelessness or documented flea bites.

The most sobering number came from the immunologically weakest participants. Among the 34 patients with CD4 counts below 200 cells per microliter, 28, or 82 percent, were seropositive for at least one Bartonella antibody class. The authors are careful to note that serology alone cannot establish clinically relevant infection or prove a causal link with immunodeficiency, since IgG positivity reflects past exposure and IgM may signal recent infection that molecular testing would be needed to confirm. Still, the figure aligns with international data: seroprevalence among HIV-infected populations has ranged from 17.3 to 40 percent in prior studies, with a Spanish study reporting 22.3 percent, a Brazilian study 40.8 percent, and a South African molecular study detecting bartonellosis in 10 percent of HIV-positive outpatients.

The authors also confront the inherent limits of antibody-based detection. IFA sensitivity ranges from 50 to 95 percent, and cross-reactivity with Coxiella, Chlamydia, and potentially Mycobacterium species, which are common in HIV patients, can blur specificity. In advanced immunosuppression, impaired humoral responses may blunt antibody production entirely, producing false negatives despite active infection, which means negative serology cannot exclude Bartonella in severely immunocompromised patients. The absence of PCR confirmation in this study likewise prevents a clean separation of past from recent exposure and may have led to slight underestimation of recent infections. When treatment is needed, current evidence favors macrolides such as azithromycin, tetracyclines, particularly doxycycline, and rifampin, which carry the most reliable minimum inhibitory concentration data, having displaced the beta-lactams used historically.

The broader message is one of vigilance rather than alarm. Exposure to Bartonella species appears common in both HIV-infected and non-infected Iranians, and the combination of molecular and serological evidence, including a companion PCR study that detected B. quintana exclusively among immunocompromised patients, supports active circulation of these bacteria in vulnerable populations. The authors argue that the healthcare community should pay closer attention to bartonellosis surveillance and management in people with HIV, particularly those with advanced immunosuppression, and that standardized diagnostic approaches combining serology with molecular methods are critically important. As the study’s findings make clear, a bacterium once associated with trench warfare and stray cats has not disappeared; it has simply been waiting for immune systems to falter.

Subject of Research: Seroprevalence of Bartonella quintana and Bartonella henselae antibodies among HIV-positive patients in Iran

Article Title: A cross sectional seroprevalence study of Bartonella quintana and Bartonella henselae among patients with human immunodeficiency virus (HIV) in Iran

Article References: Latifian, M., Hasannezhad, M., Abbasian, L., Tahmasebi Ashtiani, Z., Arabian, M., Bagheri Amiri, F., & Esmaeili, S. (2026). A cross sectional seroprevalence study of Bartonella quintana and Bartonella henselae among patients with human immunodeficiency virus (HIV) in Iran. New Microbes and New Infections, 73, Article 101841. https://doi.org/10.1016/j.nmni.2026.101841

Image Credits: AI Generated

DOI: Not provided

Keywords: Bartonella quintana, Bartonella henselae, HIV, seroprevalence, immunocompromised patients, cat scratch disease, trench fever, immunofluorescence assay, Iran, opportunistic infection, vector-borne bacteria, CD4 count