Unmasking Bartonella henselae infection in the shadows of long COVID thanks to clinical metagenomics.

The diagnosis of long COVID often relies on symptoms post-COVID-19, occasionally lacking biological evidence. This case study illustrates how investigating long COVID uncovered an underlying bartonellosis through clinical metagenomics. Following mild COVID-19, a 26-year-old woman experienced persistent symptoms during 5 months, including axillary adenopathy. Pathological examination, 16 S rRNA PCR, and clinical metagenomic analysis were done on an adenopathy biopsy. The latter revealed Bartonella henselae DNA and RNA. Treatment with clarithromycin improved symptoms. This case underscores the relevance of clinical metagenomics in diagnosing hidden infections. Post-COVID symptoms warrant thorough investigation, and bartonellosis should be considered in polyadenopathy cases, regardless of a recent history of cat or flea exposures.

Epidemiology and treatment of invasive Bartonella spp. infections in the United States.

OBJECTIVES: Bartonella spp., renowned for cat-scratch disease, has limited reports of dissemination. Tissue and blood cultures have limitations in detecting this fastidious pathogen. Molecular testing (polymerase chain reaction, PCR) and cell-free DNA have provided an avenue for diagnoses. This retrospective observational multicenter study describes the incidence of disseminated Bartonella spp. and treatment-related outcomes. METHODS: Inclusion criteria were diagnosis of bartonellosis via diagnosis code, serology testing of blood, polymerase chain reaction (PCR) of blood, 16/18S tests of blood or tissue, cultures of blood or tissue, or cell-free DNA of blood or tissue from January 1, 2014, through September 1, 2021. Exclusions were patients who did not receive treatment, insufficient data on treatment course, absence of dissemination, or retinitis as dissemination. RESULTS: Patients were primarily male (n = 25, 61.0%), white (n = 28, 68.3%), with mean age of 50 years (SD 14.4), and mean Charlson comorbidity index of 3.5 (SD 2.1). Diagnosis was primarily by serology (n = 34, 82.9%), with Bartonella henselae (n = 40, 97.6%) as the causative pathogen. Treatment was principally doxycycline with rifampin (n = 17, 41.5%). Treatment failure occurred in 16 (39.0%) patients, due to escalation of therapy during treatment (n = 5, 31.3%) or discontinuation of therapy due to an adverse event or tolerability (n = 5, 31.3%). CONCLUSIONS: In conclusion, this is the largest United States-based cohort of disseminated Bartonella spp. infections to date with a reported 39% treatment failure. This adds to literature supporting obtaining multiple diagnostic tests when Bartonella is suspected and describes treatment options.

Molecular and Serological Survey of the Cat-Scratch Disease Agent (Bartonella henselae) in Free-Ranging Leopardus geoffroyi and Leopardus wiedii (Carnivora: Felidae) From Pampa Biome, Brazil.

The genus Bartonella comprises emerging bacteria that affect humans and other mammals worldwide. Felids represent an important reservoir for several Bartonella species. Domestic cats are the main reservoir of Bartonella henselae, the agent of cat scratch disease (CSD). It can be transmitted directly by scratches and bites from infected cats and via cat fleas. This study aims to investigate the circulation of Bartonella spp. in free-ranging Neotropical wild felids from Southern Brazil using serological and molecular methods. In this study, 53 live-trapped free-ranging wild felids were sampled, 39 Leopardus geoffroyi and 14 Leopardus wiedii, from five municipalities in the Rio Grande, do Sul state, southern Brazil. All captured animals were clinically healthy. Two blood samples of L. geoffroyi were positive, by PCR, for the presence of B. henselae DNA. Conversely, none of L. wiedii blood samples were positive when tested using PCR. Indirect immunofluorescence assay (IFA) showed that 28% of serum samples of wild felids were reactive (seropositive) for B. henselae by immunofluorescence, with titers ranging from 64 to 256. The results presented here provide the first evidence of a Bartonella-enzootic cycle involving L. geoffroyi and L. wiedii, which may account for the spillover of the emerging zoonotic pathogen B. henselae for the indigenous fauna in Southern Brazil.

Posterior Segment Manifestations of Cat-scratch Disease: A Mini-review of the Clinical and Multi-modal Imaging Features.

Bartonella henselae, an intracellular gram-negative bacillus, is usually transmitted from infected cats to humans by direct or indirect contact. The bacterium mainly infects erythrocytes and endothelial cells thereby leading to so called cat-scratch disease (CSD) and may present with various localised and/or systemic manifestations. The eye is the most commonly affected organ in disseminated CSD and ocular bartonellosis has been reported in 5-10% of CSD patients. The most well-known clinical feature of ocular bartonellosis is neuroretinitis but various sight-threatening posterior segment lesions involving the optic nerve, retinal vasculature, retinal and choroidal tissues may occur during the disease course. This mini-review aims to overview both the clinical and multi-modal imaging characteristics of posterior ocular segment manifestations of CSD.

Disseminated Bartonella henselae disease mimicking Langerhans' cell histiocytosis.

Bartonella henselae, the causative agent of cat-scratch disease, has been recognized to be responsible for a broad range of clinical syndromes. We report the case of a patient with disseminated B. henselae infection mimicking Langerhans cell histiocytosis at presentation and its successful management with neurosurgery, prolonged antibacterial therapy, and observation.

Whole-Genome Analysis of Bartonella ancashensis, a Novel Pathogen Causing Verruga Peruana, Rural Ancash Region, Peru.

The genus Bartonella contains >40 species, and an increasing number of these Bartonella species are being implicated in human disease. One such pathogen is Bartonella ancashensis, which was isolated in blood samples from 2 patients living in Caraz, Peru, during a clinical trial of treatment for bartonellosis. Three B. ancashensis strains were analyzed by using whole-genome restriction mapping and high-throughput pyrosequencing. Genome-wide comparative analysis of Bartonella species showed that B. ancashensis has features seen in modern and ancient lineages of Bartonella species and is more related to B. bacilliformis. The divergence between B. ancashensis and B. bacilliformis is much greater than what is seen between known Bartonella genetic lineages. In addition, B. ancashensis contains type IV secretion system proteins, which are not present in B. bacilliformis. Whole-genome analysis indicates that B. ancashensis might represent a distinct Bartonella lineage phylogenetically related to B. bacilliformis.

Shifts in the ecological niche of Lutzomyia peruensis under climate change scenarios in Peru.

The Peruvian Andes presents a climate suitable for many species of sandfly that are known vectors of leishmaniasis or bartonellosis, including Lutzomyia peruensis (Diptera: Psychodidae), among others. In the present study, occurrences data for Lu. peruensis were compiled from several items in the scientific literature from Peru published between 1927 and 2015. Based on these data, ecological niche models were constructed to predict spatial distributions using three algorithms [Support vector machine (SVM), the Genetic Algorithm for Rule-set Prediction (GARP) and Maximum Entropy (MaxEnt)]. In addition, the environmental requirements of Lu. peruensis and three niche characteristics were modelled in the context of future climate change scenarios: (a) potential changes in niche breadth; (b) shifts in the direction and magnitude of niche centroids, and (c) shifts in elevation range. The model identified areas that included environments suitable for Lu. peruensis in most regions of Peru (45.77%) and an average altitude of 3289 m a.s.l. Under climate change scenarios, a decrease in the distribution areas of Lu. peruensis was observed for all representative concentration pathways. However, the centroid of the species' ecological niche showed a northwest direction in all climate change scenarios. The information generated in this study may help health authorities responsible for the supervision of strategies to control leishmaniasis to coordinate, plan and implement appropriate strategies for each area of risk, taking into account the geographic distribution and potential dispersal of Lu. peruensis.

DETECTION OF BARTONELLA SP. IN DEER LOUSE FLIES (LIPOPTENA MAZAMAE) ON GRAY BROCKET DEER (MAZAMA GOUAZOUBIRA) IN THE NEOTROPICS.

Louse flies or deer keds, Lipoptena spp., are widespread in Neotropical cervids, but the vector-borne pathogens of louse flies had only been previously reported in the Northern hemisphere. This is the first report of Bartonella spp. in deer louse flies (Lipoptena mazamae) in the neotropics collected from gray brocket deer ( Mazama gouazoubira ) in Southern Brazil. DNA from Bartonella sp. was detected in all 429 L. mazamae collected from 11 road-killed gray brocket deer. The same sequences of DNA of Bartonella spp. were identified in samples. Gray brocket deer are abundant in Brazil, so Bartonella-infected Lipoptena spp. may be widely distributed in the neotropics.

Ocular bartonellosis in transplant recipients: two case reports and review of the literature.

Cat scratch disease is caused by Bartonella henselae and usually manifests as localized lymphadenopathy and fever in immunocompetent patients. Immunocompromised patients are at risk for developing disseminated disease affecting the liver, spleen, eyes, central nervous system, and other organs. Bartonellosis is infrequently reported in solid organ transplant recipients, and published case reports usually discuss disseminated infection. Localized ocular disease with B. henselae, while well documented in immunocompetent hosts, is uncommon in immunocompromised patients. Herein, we present 2 cases of ocular bartonellosis in renal transplant patients, 1 with disseminated infection, and 1 without.

Molecular evidence of Bartonella spp. in tropical wild birds from the Brazilian Pantanal, the largest wetland in South America.

Despite the worldwide occurrence of bartonellae in a broad range of mammal species, in which they usually cause a long-lasting erythrocytic bacteremia, few studies reported Bartonella spp. in avian hosts. The present work aimed to investigate the occurrence and molecular identity of Bartonella spp. infecting birds in the Pantanal wetland, central-western Brazil using a multigene approach. For this purpose, blood samples were collected from 517 individuals from 13 avian orders in the states of Mato Grosso and Mato Groso do Sul. DNA was extracted from avian blood and 500/517 (96.7%) samples were positive in a conventional PCR targeting the avian ß-actin gene. Nineteen (3.8%) out of 500 avian blood samples were positive in a qPCR assay for Bartonella spp. based on the nuoG gene. Among 19 avian blood DNA samples positive in the qPCR for Bartonella spp., 12 were also positive in the qPCR for Bartonella based on the 16S-23S RNA Intergenic region (ITS). In the PCR assays performed for molecular characterization, one 16S rRNA, three ribC, and one nuoG sequences were obtained. Based on BLASTn results, while 1 nuoG, 2 ribC, and 2 ITS sequences showed high identity to Bartonella henselae, one 16S rRNA and 2 ITS showed high similarity to Bartonella machadoae in the sampled birds. Bartonella spp. related to B. henselae and B. machadoae were detected, for the first time, in wild birds from the Brazilian Pantanal.

Geographical distribution of Bartonella spp in the countries of the WHO Eastern Mediterranean Region (WHO-EMRO).

Bartonellosis is a vector-borne and zoonotic diseases in humans, especially in immunocompromised individuals. However, there is no complete data about the geographical distribution of different species of Bartonella, as well as the status of its reservoirs, vectors, and human cases in most parts of the world. In this study, published reports related to Bartonella species from WHO-EMRO region countries were searched in different databases until October 2023. The eighteens different species of Bartonella were reported in WHO-EMRO countries including Bartonella henselae, Bartonella quintana, Bartonella elizabethae, Bartonella bovis, Bartonella clarridgeiae, Bartonella vinsonii, Bartonella doshiae, Bartonella taylorii, Bartonella rochalimae, Bartonella tribocorum, Bartonella rattimassiliensis, candidatus Bartonella merieuxii, candidatus Bartonella dromedarii, Bartonella acomydis, Bartonella jaculi, Bartonella coopersplainsensis and Bartonella koehlerae. Also, only human cases of B. henselae and B. quintana infections were reported from WHO-EMRO countries. The infections of Bartonella are important in the WHO-EMRO region, but they have been neglected by clinicians and healthcare systems.

Bartonella Henselae Related Unilateral Anterior Uveitis and Subsequent Multifocal Retinitis in a Case Under Certolizumab Treatment.

Introduction: A case of ocular bartonellosis under anti-tumour necrosis factor treatment is described. Case description: A 29-year-old woman with psoriasis who had been on certolizumab treatment was examined with a left visual deterioration following a fever bout, malaise, and placoid erythematous rashes on her neck. As there was acute anterior uveitis in her left eye, it was recommended to stop certolizumab treatment for a possible infectious aetiology. However, her physician elected to continue the certolizumab treatment. Ten days later, the patient noticed further visual decline despite the topical steroid treatment. This time, there were scattered yellow-white small retinitis foci at the left posterior pole. Infectious agents were searched and while Bartonella henselae antibodies were negative for immunoglobulin M, the immunoglobulin G titre was 1/80. Clinical findings were improved with the systemic treatment of oral trimethoprim-sulfamethoxazole (160/800 mg twice daily for six weeks) and azithromycin (500 mg once daily for two weeks). Discussion: Though extremely rare, ocular bartonellosis should be kept in mind in patients on anti-tumour necrosis factor treatment as rapid and accurate diagnosis may end up with an excellent visual outcome and full recovery. LEARNING POINTS: Anti-tumour necrosis factor treatment is fraught with several ocular side effects including myositis, corneal infiltrates, scleritis, uveitis, optic neuritis, retinal vasculitis and ophthalmoplegia.When a new uveitis episode occurs in cases undergoing anti-tumour necrosis factor therapy, its cause poses a diagnostic challenge as it can have either an infectious or a non-infectious nature.Though very rare, ocular bartonellosis may also occur in immunocompromised individuals and a prompt diagnosis and appropriate treatment can lead to an excellent visual recovery.

Bartonella- and Borrelia-Related Disease Presenting as a Neurological Condition Revealing the Need for Better Diagnostics.

The diagnostic tests available to identify vector-borne pathogens have major limitations. Clinicians must consider an assortment of often diverse symptoms to decide what pathogen or pathogens to suspect and test for. Even then, there are limitations to the currently available indirect detection methods, such as serology, or direct detection methods such as molecular tests with or without culture enrichment. Bartonella spp., which are considered stealth pathogens, are particularly difficult to detect and diagnose. We present a case report of a patient who experienced a spider bite followed by myalgia, lymphadenopathy, and trouble sleeping. She did not test positive for Bartonella spp. through clinically available testing. Her symptoms progressed and she was told she needed a double hip replacement. Prior to the surgery, her blood was submitted for novel molecular testing, where Bartonella spp. was confirmed, and a spirochete was also detected. Additional testing using novel methods over a period of five years found Bartonella henselae and Borrelia burgdorferi in her blood. This patient's case is an example of why new diagnostic methods for vector-borne pathogens are urgently needed and why new knowledge of the variable manifestations of Bartonellosis need to be provided to the medical community to inform and heighten their index of suspicion.

Epidemiology of feline bartonellosis and molecular characteristics of Bartonella henselae in Bangladesh.

Bartonellosis, a neglected vector-borne zoonotic disease transmitted from animals to humans, continues to threaten human and animal health significantly. This study aims to determine the epidemiology of feline bartonellosis and the molecular characteristics of Bartonella spp. in cats. From June 2018 to June 2020, 304 oral swabs were randomly collected from Bangladesh's Dhaka, Mymensingh, and Rajshahi districts. A pre-tested questionnaire was administered to collect data. Oral swabs were subjected to PCR targeting htrA gene to confirm Bartonella spp., which was subsequently validated through sequencing. Risk factors were identified using multivariable logistic regression analysis. The overall prevalence of feline bartonellosis was found to be 15.1 %. The following factors were significantly (p < 0.05) associated with Bartonella infection in risk factor analysis: cats aged ≥ 1 year (OR: 3.23, 95 % CI: 1.38-24.40), local breed cats (OR: 3.37, 95 % CI: 1.05-10.81), cats carrying fleas (OR: 2.33, 95 % CI: 1.93-13.45), antifleacidal drugs inconsistently administered cats (OR: 6.74, 95 % CI: 3.17-14.31), outdoor access cats (OR: 2.54, 95 % CI: 1.16-5.57). Notably, zoonotic B. henselae was confirmed through sequencing, establishing it as the causal agent of cat scratch disease. Phylogenetic analysis showed homology with B. henselae sequences from Brazil, Saint Kitts, and Nevis. We recommend consistent and appropriate flea control measures to curb its spread among Bangladeshi cats. Moreover, limiting outdoor exposure or implementing preventive measures for outdoor cats could reduce the disease burden. The associated human health risk can be decreased by effectively controlling this disease within the cat population.

Molecular detection and characterization of Bartonella spp. in small mammals in the Amazonia and Cerrado biomes, midwestern Brazil.

Although Bartonella spp. have been worldwide described in rodents and bats, few studies have reported these agents in marsupials. The present work aimed to investigate the occurrence and genetic diversity of Bartonella in small mammals (rodents, marsupials, and bats) and associated ectoparasites in two ecoregions (Amazonia and Cerrado biomes) in midwestern Brazil. For this purpose, DNA samples from 378 specimens of small mammals (128 rodents, 111 marsupials, and 139 bats) and 41 fleas (Siphonaptera) were screened for the Bartonella genus employing a quantitative real-time PCR assay (qPCR) based on the nuoG (nicotinamide adenine dinucleotide dehydrogenase gamma subunit) gene. Then, positive samples in qPCR were submitted to conventional PCR (cPCR) assays targeting the gltA, ftsZ, and rpoB genes. One (0.78 %) rodent, 23 (16.54 %) bats, and 3 (7.31 %) fleas showed positive results in the qPCR for Bartonella sp. After cPCR amplification and sequencing, 13 partial Bartonella DNA sequences of the following genes were obtained only from bats´ blood samples: 9 gltA (citrate synthase), 3 ftsZ (cell division protein), and 1 rpoB (RNA polymerase beta subunit). The maximum likelihood inference based on the gltA gene positioned the obtained sequences in three different clades, closely related to Bartonella genotypes previously detected in other bat species and bat flies sampled in Brazil and other countries from Latin America. Similarly, the ftsZ sequences clustered in two different clades with sequences described in bats from Brazil, other countries from Latin America, and Georgia (eastern Europe). Finally, the Bartonella rpoB from a specimen of Lophostoma silvicolum clustered with a Bartonella sp. sequence obtained from a Noctilio albiventris (KP715475) from French Guiana. The present study provided valuable insights into the diversity of Bartonella genotypes infecting bats from two ecoregions (Amazonia and Cerrado) in midwestern Brazil and emphasized that further studies should be conducted regarding the description and evaluation of different lineages of Bartonella in wild small mammals and their ectoparasites in different Brazilian biomes.

Combining Double-Dose and High-Dose Pulsed Dapsone Combination Therapy for Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome and Co-Infections, Including Bartonella: A Report of 3 Cases and a Literature Review.

Three patients with relapsing and remitting borreliosis, babesiosis, and bartonellosis, despite extended anti-infective therapy, were prescribed double-dose dapsone combination therapy (DDDCT) for 8 weeks, followed by one or several two-week courses of pulsed high-dose dapsone combination therapy (HDDCT). We discuss these patients' cases to illustrate three important variables required for long-term remission. First, diagnosing and treating active co-infections, including Babesia and Bartonella were important. Babesia required rotations of multiple anti-malarial drug combinations and herbal therapies, and Bartonella required one or several 6-day HDDCT pulses to achieve clinical remission. Second, all prior oral, intramuscular (IM), and/or intravenous (IV) antibiotics used for chronic Lyme disease (CLD)/post-treatment Lyme disease syndrome (PTLDS), irrespective of the length of administration, were inferior in efficacy to short-term pulsed biofilm/persister drug combination therapy i.e., dapsone, rifampin, methylene blue, and pyrazinamide, which improved resistant fatigue, pain, headaches, insomnia, and neuropsychiatric symptoms. Lastly, addressing multiple factors on the 16-point multiple systemic infectious disease syndrome (MSIDS) model was important in achieving remission. In conclusion, DDDCT with one or several 6-7-day pulses of HDDCT, while addressing abnormalities on the 16-point MSIDS map, could represent a novel effective clinical and anti-infective strategy in CLD/PTLDS and associated co-infections including Bartonella.

Novel Bartonella agent as cause of verruga peruana.

While studying chronic verruga peruana infections in Peru from 2003, we isolated a novel Bartonella agent, which we propose be named Candidatus Bartonella ancashi. This case reveals the inherent weakness of relying solely on clinical syndromes for diagnosis and underscores the need for a new diagnostic paradigm in developing settings.

Molecular evidence of Bartonella spp. in wild lowland tapirs (Tapirus terrestris), the largest land mammals in Brazil.

The genus Bartonella (Hyphomicrobiales: Bartonellaceae) encompasses facultative intracellular α-proteobacteria that parasite erythrocytes and endothelial cells from a wide range of vertebrate hosts and can cause disease in animals and humans. Considering the large diversity of vertebrate species that may act as reservoirs and arthropod species that may be associated with Bartonella transmission, the exposure of animals and humans to these microorganisms is likely underestimated. The present study aimed to investigate the occurrence of Bartonella sp. in wild tapirs (Tapirus terrestris; Perissodactyla: Tapiridae) from two biomes in Brazil: Pantanal and Cerrado. Ninety-nine GPS-monitored wild tapirs were sampled in Pantanal (n = 61/99) and Cerrado (n = 38/99). A qPCR (quantitative real-time polymerase chain reaction) assay targeting the nuoG gene was used for the screening for Bartonella spp. DNA. Positive samples were additionally subjected to conventional PCR assays targeting five molecular markers (ribC, gltA, rpoB, groEL, ITS). Eight (8/99; 08,08%) animals were positive in the qPCR assay for Bartonella spp.: 7 from Cerrado (7/8; 87.5%) and 1 from Pantanal (1/8; 12.5%). The 5 Bartonella ribC sequences obtained from tapirs' blood samples grouped together with Bartonella henselae obtained from cats, humans, wild felids and Ctenocephalides felis (Siphonaptera: Pulicidae) fleas. To the best of author's knowledge, this is the first report of Bartonella sp. in Tapirus terrestris. This finding contributes to the understanding of the occurrence of B henselae in wild mammals from Brazil as well as expands the knowledge regarding the potential vector-borne pathogens that may affect wild tapis from Cerrado and Pantanal biomes.

Multi-locus Sequencing Typing of Bartonella henselae isolates reveals coinfection with different variants in domestic cats from Midwestern Brazil.

Bartonella henselae is a zoonotic pathogen responsible for causing Cat Scratch Disease (CSD) and other clinical manifestations in humans. Domestic cats are the main reservoirs of this Bartonella species. Previous studies have suggested that certain genotypes of B. henselae seem to be more associated with human infections. The present study aimed to genotype B. henselae isolates from domestic cats' blood samples in the state of Goiás, midwestern Brazil. The association of quantitative real-time PCR (qPCR) based on the nuoG gene from Bartonella spp. of blood samples, before and after incubation in pre-enrichment liquid medium (BAPGM) and isolation on chocolate agar, showed a positivity frequency of 42% (42/100) for Bartonella spp. Twelve B. henselae isolates obtained on agar chocolate from six cats' blood samples (two isolates from each animal) were characterized by Multi-locus Sequencing Typing (MLST) and revealed to belong to Sequence Types ST1 and ST5. One of the cats (1/6) presented both STs, demonstrating that domestic cats can be coinfected with different variants of B. henselae. The STs detected in this study are distributed worldwide and have already been detected in humans with clinical manifestations of bartonellosis. This is the first report of the zoonotic variants ST1 and ST5 of B. henselae in domestic cats from Brazil.