Background
Infective endocarditis (IE) is a life-threatening systemic infectious disease in which a multidisciplinary group of specialists is required for patient treatment and follow-up.
Viridans streptococci,
Streptococcus bovis,
Haemophilus spp.,
Aggregatibacter spp.,
Cardiobacterium hominis,
Eikenella corrodens, and
Kingella spp. (HACEK) group,
Staphylococcus aureus, or community-acquired enterococci are classic typical microorganisms causing IE, an infection associated with the proliferation of microorganisms on the endocardium [
1]. Vegetation is the prototypic lesion of IE, which can be identified by a mass of platelets, fibrin, and microcololia of bacteria, fungi, or other germs and scant inflammatory cells. The vegetation of IE is located on the mural endocardium and analogous processes can occur in intracardiac devices, arteriovenous shunts, or coarctation of the aorta [
2]. The risk factors of IE involve patients with predisposing heart conditions and comorbidities, including intravenous drug use, among other factors [
3]. The diagnosis of IE is established according to the modified Duke criteria [
1,
4], which include predisposing heart condition or intravenous drug use, symptoms such as fever ≥ 38 °C, vascular phenomena, immunologic phenomena, and serologic evidence of active infection consistent with IE or positive blood culture but not meeting major criteria [
1,
2,
4,
5]. Major modified Duke criteria, in addition to including the persistently positive blood culture and evidence of endocardial involvement, now include positive serology for
Coxiella burnetii and
Bartonella spp.
At least two separated positive blood cultures samples, with typical microorganisms, are required to meet major microbiological criteria. Gram-negative bacillus such as
Bartonella spp.,
C.
burnetti, and
Tropheryma whipplei, some fungi such as
Aspergillus spp. and
Histoplasma must be searched when facing blood culture-negative infective endocarditis (BCNIE), since these etiological agents are harder to be cultivated
in vitro [
6‐
9]. Specifically,
C.
burnetti,
Bartonella quintana, and
Bartonella henselae are not easy to isolate in blood cultures, and classic Duke criteria do not identify patients with IE.
In this context, serological and molecular methods have become an important tool in the detection of
C.
burnetti and
Bartonella spp. in the last decades in Brazil. The genus
Bartonella is recognized as the second most frequent etiological agent in HACEK group, non-HACEK groups, and BCNIE.
B.
henselae is the most prevalent of the 14 species of associated with
Bartonella endocarditis. This species is also known to be the main cause of cat scratch disease (CSD), a typical zoonotic disease in Brazil [
10]. Although domestic cats and their ectoparasites are often found as hosts of
B.
henselae [
11‐
13], dogs have also been reported to host this species [
14,
15].
The risk is not limited to clinical cases in humans; dogs and cats can also develop cardiac complications related to infection by
Bartonella [
10,
16‐
20]. Bartonellosis is a disease of medical and veterinary importance, so One Health becomes a strategy to approach this epidemiological context. The One Health approach integrates a multidisciplinary team of researchers from different areas of knowledge to cooperate in the diagnosis, prevention, treatment, and mitigation of infection diseases [
21]. The most common health professionals are typically physicians, veterinarians, and biologists linking human, animal, and environmental health [
21]. Thus, the One Health epidemiological approach, such as in this study, could make more data available in the IE scenario associated with zoonoses [
19].
In Brazil, where most cases of endocarditis are found in the Southeast region, we still have few epidemiological data on
Bartonella endocarditis, although we have been working on retrospective studies since 2006 [
5,
8,
9,
22‐
24]. The aim of this report is to show two cases of
B.
henselae endocarditis associated with
Bartonella-infected domestic animals during the COVID-19 pandemic in Rio de Janeiro, in the southeast region of Brazil. We considered the modified Duke criteria to establish the diagnosis of IE caused by
Bartonella, including the presence of titer Immunoglobulin type G (IgG) antibodies against
Bartonella spp. ≥ 800 of dilution and a positive result of molecular testing obtained from cardiac valve and blood samples.
Discussion and conclusions
Bartonella infections occur worldwide and can be associated with blood culture-negative infective endocarditis (BCNIE). Since the first publication of infective endocarditis due to
Bartonella spp. confirmed by serologic test in Brazil, few cases of this endocarditis infection have been reported, although cases of cat scratch disease (CSD) are often reported, especially in the southeast Brazilian region [
8].
On the basis of clinical and diagnostic protocols in this case report, both patients met the evaluation criteria for infective endocarditis associated with blood culture-negative, a heart disease infection often severe and difficult to diagnose. In view of the inconclusive microbiological research with blood cultures, serum samples collected from the two patients and cardiac valve tissue sample (patient 1) were analyzed by both serological and molecular tests and the results confirmed infection by B. henselae. Often the Bartonella diagnosis is determined using serological tests, mainly by IFA. In this study, the patients presented high IgG-antibodies titers to Bartonella spp., a fact that allows the confirmation of BCNIE caused by this zoonotic agent exclusively by serological testing, since the IFA results with IgG titers ≥ 1:800 have a sensitivity of 90% and specificity of 99%.
Subsequent molecular analysis performed on blood and cardiac tissue (mitral valve) sample collected from patients allowed for the identification of the
B.
henselae species as the causative agent of BCNIE. Since 2009, the National Reference Laboratory for Rickettsioses/Ministry of Health (NRLR), Laboratory of Hantaviruses and Rickettsiosis, Oswaldo Cruz Institute, and FIOCRUZ, have been collaborating with our IE team at our teaching hospital. It is the first time we have
B.
henselae endocarditis in our series of 110 cases of IE defined by modified Duke criteria in Rio de Janeiro, Brazil. The incidence of BCNIE in this Brazilian cohort was 10.9%, although the frequency of BCNIE in review of IE in low- and middle-income countries during the years 2002–2017 ranged from 10.8–69.1% [
5].
These
Bartonella IE cases are a classic example of a zoonosis where a One Health approach must be applied [
19]. After the confirmation of endocarditis caused by
B.
henselae, a multidisciplinary team carried out visits at the homes of both patients. The participation of a veterinarian allowed for the handling of domestic animals, the collection of blood samples, and the search for ectoparasites in these animals. From the epidemiological inquiry, both patients maintained very close contact with the animals, living with the pets until bedtime.
Serological investigation of domestic animals showed IgG reactivity to
Bartonella spp. in the patients’ pets. Information regarding intimate contact with these pets, as well as our serological results, reinforce the likelihood of contagion through this human–pet relationship. It is interesting to consider that during the isolation caused by the SARS-CoV-2 pandemic, this contact between humans and their pets increased, which may have facilitated exposure to
B.
henselae. In this context, the presence of ectoparasites and the possibility of injury caused by scratches can facilitate the inoculation of this agent in humans [
11,
26,
27].
Despite evidence of circulation of
Bartonella spp. having already been reported in other studies from Rio de Janeiro [
9,
28], in these case reports we indicate which bacterial species was found in these patients, which facilitates the understanding of the epidemiological aspects and the investigation of human cases from a One Health initiative [
19]. The formation of a multidisciplinary team is the most effective way to identify zoonotic agents such as
Bartonella that cause infections in humans and animals, also considering the non-specificity of this bacteria genus, which can be found in humans as well as in domestic and wild animals in several different environments [
10,
19,
21,
29,
30].
Our two cases of Bartonella henselae infection exemplify two difficulties in defining Bartonella IE. Firstly, finding the vegetation in the valvular endocardium in the echocardiography proved to be very difficult. Secondly, although both patients had a subacute temporal course with weight loss and changes in kidney function, they did not have vascular phenomena. Bartonella endocarditis is a diagnostic challenge even for cardiac surgery referral centers. Health professionals should be alert to an atypical case of infective endocarditis, especially when patients have weight loss, kidney injury, and epidemiological history for domestic animals with ectoparasites.
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