Bartonellas: could they cause reproductive disorders in humans?Campinas, January 28th, 2025
Dear Editor,
Bartoneloses are millennial diseases. There are Bartonella species that have universal distribution, such as Bartonella henselae, which is the species most associated with disease in humans. Although infection by these bacteria can be fatal, as in the case of endocarditis, infected humans can also be asymptomatic, as observed in 500 blood donors from the UNICAMP Blood Bank of Campinas, Sao Paulo State, Brazil, of which more than 20% showed detection of B. henselae DNA or isolation of the bacteria, which reveals the high prevalence of infection among asymptomatic subjects1.
Although Maillard et al.2 observed no relationship between Bartonella bovis and Bartonella chomelii infection in dairy cattle herds and their offspring, different Bartonella species have already been associated with reproductive difficulties in mammals. Reproductive disorders such as abortion and fetal resorption have been described in female cats experimentally infected with B. henselae3. Guptill et al.4 experimentally demonstrated that B. henselae causes reproductive failure in female cats, but transplacental transmission was not evidenced. A recent study demonstrated that B. henselae DNA was amplified from fetal and placental samples from stray cats that were frequently positive for bacterium in reproductive tissues5.
Another study linked the presence of B. henselae to the probable cause of foal abortion, and this is the first documentation of the species causing abortion in horses6. Kosoy et al.7 isolated Bartonella species in embryos and neonates of naturally infected rodents. Subsequently, the pathogenic effect on the reproductive functions of BALB/c mice experimentally infected with Bartonella birtlesii was described by Boulouis et al.3, who demonstrated increased fetal death and lower birth weights of viable fetuses. Transplacental transmission has been documented by isolation of the bacteria from fetuses8.
Siewert et al.9 recently wrote about how the adaptive immune defense prevents Bartonella persistence in transplacental transmission in C57BL/6 mice. Furthermore, de Bruin et al.10 reported Bartonella schoenbuchensis DNA in all life stages of Lipoptena cervi ticks, except for three fully developed pupae. The DNA was found in various types of ticks, including wingless adult males and females collected from both red deer and roe deer, as well as in larvae harvested from adult females. This reinforces the notion that Bartonella is transmitted vertically from wingless females to larvae that will develop into pupae.
We understand that from a One Health perspective, Bartonella spp. infection may be related to immunoprotection or immunoaggression via the vertical route in humans as well, as described for the animals studied by the authors. They cite vertical transmission of Bartonella sp. in small rodents9, but also in humans in the case reported by Breitschwerdt et al.8. In this report, the possible transmission of B. henselae and Bartonella vinsonii subsp. berkhoffii from a woman to her twin sons, conceived after in vitro fertilization, was found. One of the newborns died nine days after birth due to hypoplastic left heart syndrome. Bartonella sp. DNA was detected in the blood and/or paraffin tissue of the four family members: the woman, her husband, and the twins. The authors point out that since there were difficulties for the woman to become pregnant naturally, which persisted after consecutive in vitro fertilizations, the case highlights the possibility that Bartonella sp. infection can negatively influence human reproductive performance.
Another case reported by Velho et al.11 also reinforces the hypothesis of vertical transmission of Bartonella sp. in humans and describes a three-year-old child born to an asymptomatic woman, for whom the possibility of vertically transmitted B. henselae infection was hypothesized because the baby presented anemia, jaundice, and hepatosplenomegaly since birth. This suspicion was reinforced by transmission electron microscopy findings of the patient’s liver fragment collected during a biopsy performed at 12 days of life and molecular detection by species-specific reaction of B. henselae DNA directly from three blood samples from the child and a blood sample from the mother. The amplifications were sequenced and found to be 100% homologous to B. henselae.
The possibility of vertical transmission of Bartonella bacilliformis has also been reported in a newborn with acute manifestation of Carrion’s bartonellosis whose mother had skin lesions characteristic of the chronic phase of the disease12.
Bilavisky et al.13 described eight pregnant women diagnosed with cat scratch disease (CSD) during a 19-year case surveillance study of this disease in Israel. One of them had a miscarriage with no documented association with bartonellosis, and the others had neither obstetric complications nor did their newborns manifest clinical expressions of bartonellosis. Agarwal et al.14, on the other hand, reported a case of liver rupture with a diagnosis of B. henselae infection caused by CSD in a 24-year-old pregnant woman.
Thus, the study by Siewert et al.9 reminds us of the need to evaluate the role of Bartonella sp. infection in women with repeat abortions and the role of transplacental transmission of these bacteria in humans in the same way as in mice, cats and horses.
REFERENCES
- 1 Drummond MR, Santos LS, Almeida AR, Lins KA, Barjas-Castro ML, Diniz PP, et al. Comparison of molecular methods for Bartonella henselae detection in blood donors. PLoS Negl Trop Dis. 2023;17:e0011336.
- 2 Maillard R, Grimard B, Chastant-Maillard S, Chomel B, Delcroix T, Gandoin C, et al. Effects of cow age and pregnancy on Bartonella infection in a herd of dairy cattle. J Clin Microbiol. 2006;44:42-6.
- 3 Boulouis HJ, Barrat F, Bermond D, Bernex F, Thibault D, Heller R, et al. Kinetics of Bartonella birtlesii infection in experimentally infected mice and pathogenic effect on reproductive functions. Infect Immun. 2001;69:5313-7.
- 4 Guptill L, Slater LN, Wu CC, Lin TL, Glickman LT, Welch DF, et al. Evidence of reproductive failure and lack of perinatal transmission of Bartonella henselae in experimentally infected cats. Vet Immunol Immunopathol. 1998;65:177-89.
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- 6 Johnson R, Ramos-Vara J, Vemulapalli R. Identification of Bartonella henselae in an aborted equine fetus. Vet Pathol. 2009;46:277-81.
- 7 Kosoy MY, Regnery RL, Kosaya OI, Jones DC, Marston EL, Childs JE. Isolation of Bartonella spp. from embryos and neonates of naturally infected rodents. J Wildl Dis. 1998;34:305-9.
- 8 Breitschwerdt EB, Maggi RG, Farmer P, Mascarelli PE. Molecular evidence of perinatal transmission of Bartonella vinsonii subsp. berkhoffii and Bartonella henselae to a child. J Clin Microbiol. 2010;48:2289-93.
- 9 Siewert LK, Dehio C, Pinschewer DD. Adaptive immune defense prevents Bartonella persistence upon trans-placental transmission. PLoS Pathog. 2022;18:e1010489.
- 10 de Bruin A, van Leeuwen AD, Jahfari S, Takken W, Földvári M, Dremmel L, et al. Vertical transmission of Bartonella schoenbuchensis in Lipoptena cervi. Parasit Vectors. 2015;8:176.
- 11 Velho PE, Bellomo-Brandão MA, Drummond MR, Magalhães RF, Hessel G, Barjas-Castro ML, et al. Bartonella henselae as a putative cause of congenital cholestasis. Rev Inst Med Trop Sao Paulo. 2016;58:56.
- 12 Tuya XL, Escalante-Kanashiro R, Tinco C, Pons MJ, Petrozzi V, Ruiz J, et al. Possible vertical transmission of Bartonella bacilliformis in Peru. Am J Trop Med Hyg. 2015;92:126-8.
- 13 Bilavsky E, Amit S, Avidor B, Ephros M, Giladi M. Cat scratch disease during pregnancy. Obstetr Gynecol. 2012;119:640-4.
- 14 Agarwal A, Joy D, Das P, Dash NR, Srivastava DN, Madhusudhan KS. Hemorrhage and rupture of an unusual benign liver lesion in pregnancy: a case report. J Clin Exp Hepatol. 2021;11:260-3.
