Bartonella henselae DNA detection in patients with type 1 leprosy reactions for more than six months.

Leprosy reactions are among the main causes of physical disability resulting from an infectious disease and can culminate in irreversible physical disabilities, therefore they should be considered a clinical emergency, as well as the elucidation of its cause. Co-infections are considered one of the main triggering causes of leprosy reactions, aggravating and maintaining these reactions for longer in these patients. After reporting a high rate of Bartonella henselae infection in patients with chronic type 2 leprosy reaction, 19/47 (40.4 %) compared to the control group, 9/50 (18.0 %), p = 0.0149, we conducted this study to observe the rate of infection by Bartonella sp. in a group of patients with chronic type 1 leprosy reactions. Blood samples from 14 patients with chronic type 1 leprosy reactions were analyzed by molecular and microbiological tests and compared. The results showed that, like patients with chronic type 2 leprosy reactions, this group of patients has a high proportion of B. henselae infection 6/14 (42.9 %), p = 0.88. We conclude that these bacteria can trigger chronic leprosy reactions and should be investigated in all chronic leprosy reactions patients. Summary Line: Our results showed that, like patients with chronic type 2 leprosy reactions, this group of patients has the same proportion of B. henselae DNA detection 6/14 (42.9 %), p = 0.88.

The influence of growth time on the identification of Bartonella henselae strains by MALDI-TOF mass spectrometry.

Bartonella spp. are bacteria responsible for neglected diseases worldwide. Bartonella henselae is the species most associated with human infections. It is associated with a large spectrum of clinical manifestations and is potentially fatal. The identification of Bartonella spp. is considered a challenge in clinical routine. These bacteria are fastidious, and the time required to isolate them varies from one to six weeks. MALDI-TOF mass spectrometry has emerged as an application for research on Bartonella spp. , and has still been little explored. We investigated whether three different B. henselae strains with different growth times-14 and 28 days-could be correctly identified by MALDI-TOF mass spectra fingerprint comparison and matching. We found that the spectra from strains with different growth times do not match each other, leading to misidentification. We suggest creating database entries with multiple spectra from strains with different growth times to increase the chances of accurate identification of Bartonella spp. by MALD-TOF MS.

Is Bartonella sp. infection relevant in hematological malignancies in HIV-negative patients? A literature review.

Bartonelloses are diseases caused by Bartonella sp., transmitted to humans by blood sucking arthropod vectors. Clinical presentations include bacillary angiomatosis, cat scratch disease and atypical forms. We performed a review of cases of bartonelloses and hematological malignancies published in HIV-negative patients. Terms used were Bartonella or Bacillary Angiomatosis and Leukemia, Lymphoma, Multiple Myeloma, or Cancer. Fifteen cases met our criteria. Clinical presentations included bacillary angiomatosis, chronic fever, chronic lymphadenopathy, osteomyelitis, neuroretinitis, chronic anemia and hepatosplenic peliosis. Fourteen patients were asymptomatic after antibiotic therapy, and one died before antibiotic treatment. Clinicians should be suspicious of Bartonella sp. infections in immunocompromised patients.

The influence of growth time on the identification of Bartonella henselae strains by MALDI-TOF mass spectrometry

ABSTRACT Bartonella spp. are bacteria responsible for neglected diseases worldwide. Bartonella henselae is the species most associated with human infections. It is associated with a large spectrum of clinical manifestations and is potentially fatal. The identification of Bartonella spp. is considered a challenge in clinical routine. These bacteria are fastidious, and the time required to isolate them varies from one to six weeks. MALDI-TOF mass spectrometry has emerged as an application for research on Bartonella spp. , and has still been little explored. We investigated whether three different B. henselae strains with different growth times—14 and 28 days—could be correctly identified by MALDI-TOF mass spectra fingerprint comparison and matching. We found that the spectra from strains with different growth times do not match each other, leading to misidentification. We suggest creating database entries with multiple spectra from strains with different growth times to increase the chances of accurate identification of Bartonella spp. by MALD-TOF MS.

Bartonella henselae as a putative trigger for chronic type 2 leprosy reactions.

Leprosy reactions are an acute inflammatory phenomenon that can arise before diagnosis, during treatment, or after cure of leprosy. These reactions are considered one of the main diseases that cause physical disabilities. Immunosuppressive treatment for these immune responses makes these patients susceptible to coinfections, which can trigger new leprosy reactions. The main objective of this study was to evaluate the occurrence of infection by Bartonella sp. in blood samples from 47 patients who had untreatable episodes of type 2 leprosy reactions for more than six months, comparing them with a control group. Cultures and molecular methods (PCR) were used. Amplicons from species-specific reactions and sequencing showed a higher prevalence of Bartonella henselae infection in patients, 19/47 (40.4 %), compared to control, 9/50 (18.0 %), p = 0.0149. Five patients accepted treatment for coinfection, and all showed improvement in leprosy reactions with treatment for B. henselae infection. We conclude that these bacteria can trigger chronic reactions of type 2 leprosy and should be investigated in these patients. SUMMARY LINE: Patients who have chronic type 2 leprosy reactions are more susceptible to Bartonella henselae infection than controls: 19/47 (40.4 %) compared 9/50 (18.0 %), p = 0.0149.

Detection of Bartonella henselae DNA in the blood of patients with livedoid vasculopathy

Abstract Background: Livedoid vasculopathy (LV) manifests as ulcers and atrophic white scars on the lower extremities. The main known etiopathogenesis is hypercoagulability with thrombus formation, followed by inflammation. Thrombophilia, collagen and myeloproliferative diseases may induce LV, but the idiopathic (primary) form predominates. Bartonella spp. may cause intra-endothelial infection and skin manifestations caused by these bacteria may be diverse, including leukocytoclastic vasculitis and ulcers. Objective: The aim of this study was to investigate the presence of bacteremia by Bartonella spp. in patients with difficult-to-control chronic ulcers diagnosed as primary LV. Methods: Questionnaires and molecular tests (conventional PCR, nested PCR and real-time PCR) were applied and liquid and solid cultures were performed in the blood samples and blood clot of 16 LV patients and 32 healthy volunteers. Results: Bartonella henselae DNA was detected in 25% of LV patients and in 12.5% of control subjects but failed to reach statistically significant differences (p = 0.413). Study limitations: Due to the rarity of primary LV, the number of patients studied was small and there was greater exposure of the control group to risk factors for Bartonella spp. infection. Conclusion: Although there was no statistically significant difference between the groups, the DNA of B. henselae was detected in one of every four patients, which reinforces the need to investigate Bartonella spp. in patients with primary LV.

Comparison of molecular methods for Bartonella henselae detection in blood donors.

The Bartonella genus consists of neglected pathogens associated with potentially transfusional-transmitted and fatal human diseases. We aimed to evaluate Bartonella sp. prevalence in 500 blood donors and compare the results with the data already published about these samples. We used molecular diagnostic methods to detect Bartonella sp.-DNA from blood and liquid culture samples: (A) conventional PCR for two gene regions, the ITS targeting the genus Bartonella and the specific gltA Bartonella henselae; (B) nested PCR for the ftsZ gene and (C) qualitative real-time PCR for the gltA gene, both B. henselae specific. We obtained 30/500 (6%) DNA detections from the blood samples; 77/500 (15.4%) DNA detections from liquid culture samples and five (1%) samples had DNA detection from both. In total, we detected B. henselae DNA from 102/500 (20.4%) donors. The samples used in this study had already been submitted for Bartonella sp.-DNA detection using only a conventional PCR in liquid culture. Sixteen samples (3.2%) were positive previously, and from these 16 samples, 13 were negative in the new investigation. We concluded that the use of liquid culture combined with different molecular tests increases the possibility of detecting Bartonella sp.-DNA, but the tests do not avoid false-negative results. More than a fifth of blood donors had at least one PCR that detected Bartonella sp.-DNA among the eight molecular reactions performed now (four reactions in whole blood and four in liquid culture). Seven percent had B. henselae-DNA detection for two or more distinct regions. Considering the results obtained previously, the DNA of Bartonella spp. was detected or the agent isolated in 23% of analyzed blood donors. The results establish that the low bacteremia and the fastidious characteristics of the bacterium are challenges to laboratory diagnosis and can make it difficult to confirm the infection in patients with bartonelloses.

Detection of Bartonella henselae DNA in the blood of patients with livedoid vasculopathy.

BACKGROUND: Livedoid vasculopathy (LV) manifests as ulcers and atrophic white scars on the lower extremities. The main known etiopathogenesis is hypercoagulability with thrombus formation, followed by inflammation. Thrombophilia, collagen and myeloproliferative diseases may induce LV, but the idiopathic (primary) form predominates. Bartonella spp. may cause intra-endothelial infection and skin manifestations caused by these bacteria may be diverse, including leukocytoclastic vasculitis and ulcers. OBJECTIVE: The aim of this study was to investigate the presence of bacteremia by Bartonella spp. in patients with difficult-to-control chronic ulcers diagnosed as primary LV. METHODS: Questionnaires and molecular tests (conventional PCR, nested PCR and real-time PCR) were applied and liquid and solid cultures were performed in the blood samples and blood clot of 16 LV patients and 32 healthy volunteers. RESULTS: Bartonella henselae DNA was detected in 25% of LV patients and in 12.5% of control subjects but failed to reach statistically significant differences (p = 0.413). STUDY LIMITATIONS: Due to the rarity of primary LV, the number of patients studied was small and there was greater exposure of the control group to risk factors for Bartonella spp. CONCLUSION: Although there was no statistically significant difference between the groups, the DNA of B. henselae was detected in one of every four patients, which reinforces the need to investigate Bartonella spp. in patients with primary LV.

Bartonella henselae as a putative trigger for chronic type 2 leprosy reactions

Abstract Leprosy reactions are an acute inflammatory phenomenon that can arise before diagnosis, during treatment, or after cure of leprosy. These reactions are considered one of the main diseases that cause physical disabilities. Immunosuppressive treatment for these immune responses makes these patients susceptible to coinfections, which can trigger new leprosy reactions. The main objective of this study was to evaluate the occurrence of infection by Bartonella sp. in blood samples from 47 patients who had untreatable episodes of type 2 leprosy reactions for more than six months, comparing them with a control group. Cultures and molecular methods (PCR) were used. Amplicons from species-specific reactions and sequencing showed a higher prevalence of Bartonella henselae infection in patients, 19/47 (40.4 %), compared to control, 9/50 (18.0 %), p= 0.0149. Five patients accepted treatment for coinfection, and all showed improvement in leprosy reactions with treatment for B. henselae infection. We conclude that these bacteria can trigger chronic reactions of type 2 leprosy and should be investigated in these patients. Summary line Patients who have chronic type 2 leprosy reactions are more susceptible to Bartonella henselae infection than controls: 19/47 (40.4 %) compared 9/50 (18.0 %), p= 0.0149.

Cryptogenic hepatitis patients have a higher Bartonella sp.-DNA detection in blood and skin samples than patients with non-viral hepatitis of known cause.

BACKGROUND: This study aimed to assess the prevalence of Bartonella sp.-DNA detection in blood and skin samples from patients with non-viral end-stage liver disease awaiting liver transplantation. METHODOLOGY/PRINCIPAL FINDINGS: Blood samples and healthy skin fragments from 50 patients were tested using microbiological and molecular methods. Fifteen patients had cryptogenic hepatitis (CH) and 35 had alcoholic, drug-induced or autoimmune liver disease. DNA was extracted from whole blood and liquid culture samples, isolates, and skin fragments. Thirteen of the 50 patients (26%) had Bartonella henselae DNA detection in their blood (9/50) and/or skin (5/50) samples. Colonies were isolated in 3/50 (6%) and infection was detected in 7/50 (14%) of the 50 patients. B. henselae-DNA detection was more prevalent in patients with CH than in other patients (p = 0.040). Of 39 patients followed-up for at least two years, a higher mortality rate was observed among patients with CH infected with B. henselae (p = 0.039). CONCLUSIONS/SIGNIFICANCE: Further studies assessing the role of B. henselae infection in the pathogenesis of hepatitis patients must be urgently conducted.

Two-year history of lymphadenopathy and fever caused by Bartonella henselae in a child.

We report the case of a 6-year-old boy that presented with enlarged lymph nodes on his neck. He complained of tiredness and discouragement, which worsened during feverish periods. There were no relevant laboratory test abnormalities and serological tests were not reactive. Bartonella henselae DNA was detected by species-specific nested polymerase chain reaction. After treatment, the patient progressed with no fever or lymphadenopathy. Bartonellosis is a group of infectious diseases caused by bacteria of the genus Bartonella. This case report is a useful reminder to clinicians that long-term fever of unknown origin can be related to B. henselae infection, even if the specific serology is not reactive.

Chronic type 2 reaction possibly triggered by an asymptomatic Bartonella henselae infection in a leprosy patient.

As leprosy and leprosy reactions are the most prevalent infectious cause of physical disability, it is important to commit efforts to better understand these chronic reactions. Infections, even when asymptomatic, can trigger leprosy reactions and Bartonella spp. in turn, can cause chronic infections. We presented a case of a 51-year-old man who was admitted presenting with chronic type 2 leprosy reactions. He had a lepromatous form of leprosy that was histologically diagnosed six months after the onset of signs and symptoms compatible with a chronic type 2 reaction. He reported a history of a previous hepatitis B diagnosis. During a 24-month multidrug therapy (MDT), chronic reactions were partially controlled with prednisone and thalidomide. Thirty-three months following the leprosy treatment, he still experienced chronic reactions, and whole bacilli as well as globi were found on a new skin biopsy. Since coinfections can trigger type 2 reactions and the patient had close contact with animals and ticks, we investigated the presence of a Bartonella sp. infection. Bartonella henselae DNA was detected in a skin fragment obtained before the beginning of the leprosy retreatment. However, even after six months of a second leprosy MDT, he continued to experience type 2 chronic reactions. He was admitted to the hospital to undergo an intravenous antibiotic therapy for 14 days and then complete the treatment per os for ten more weeks. Leprosy reactions improved following the treatment for B. henselae. After completing the MDT treatment, he has been accompanied for sixty months with no signs of leprosy or leprosy reactions. The asymptomatic infection by B. henselaein this patient was considered the putative trigger of chronic leprosy reactions and leprosy relapse.

Chronic type 2 reaction possibly triggered by an asymptomatic Bartonella henselae infection in a leprosy patient

ABSTRACT As leprosy and leprosy reactions are the most prevalent infectious cause of physical disability, it is important to commit efforts to better understand these chronic reactions. Infections, even when asymptomatic, can trigger leprosy reactions and Bartonella spp. in turn, can cause chronic infections. We presented a case of a 51-year-old man who was admitted presenting with chronic type 2 leprosy reactions. He had a lepromatous form of leprosy that was histologically diagnosed six months after the onset of signs and symptoms compatible with a chronic type 2 reaction. He reported a history of a previous hepatitis B diagnosis. During a 24-month multidrug therapy (MDT), chronic reactions were partially controlled with prednisone and thalidomide. Thirty-three months following the leprosy treatment, he still experienced chronic reactions, and whole bacilli as well as globi were found on a new skin biopsy. Since coinfections can trigger type 2 reactions and the patient had close contact with animals and ticks, we investigated the presence of a Bartonella sp. infection. Bartonella henselae DNA was detected in a skin fragment obtained before the beginning of the leprosy retreatment. However, even after six months of a second leprosy MDT, he continued to experience type 2 chronic reactions. He was admitted to the hospital to undergo an intravenous antibiotic therapy for 14 days and then complete the treatment per os for ten more weeks. Leprosy reactions improved following the treatment for B. henselae. After completing the MDT treatment, he has been accompanied for sixty months with no signs of leprosy or leprosy reactions. The asymptomatic infection by B. henselaein this patient was considered the putative trigger of chronic leprosy reactions and leprosy relapse.

Two-year history of lymphadenopathy and fever caused by Bartonella henselae in a child

ABSTRACT We report the case of a 6-year-old boy that presented with enlarged lymph nodes on his neck. He complained of tiredness and discouragement, which worsened during feverish periods. There were no relevant laboratory test abnormalities and serological tests were not reactive. Bartonella henselae DNA was detected by species-specific nested polymerase chain reaction. After treatment, the patient progressed with no fever or lymphadenopathy. Bartonellosis is a group of infectious diseases caused by bacteria of the genus Bartonella. This case report is a useful reminder to clinicians that long-term fever of unknown origin can be related to B. henselae infection, even if the specific serology is not reactive.

Bartonella henselae infection induces a persistent mechanical hypersensitivity in mice.

Bartonella spp. are re-emerging and neglected bacterial pathogens. The natural reservoirs for several species of this genus are domestic animals such as cats and dogs, the most common pets in the USA and Brazil. Some cat studies suggest that the infection is more prevalent in tropical and poverty-stricken areas. These bacteria were associated with a wide spectrum of clinical manifestations: fever of unknown origin, endocarditis, angiomatosis, chronic lymphadenopathy, hepatitis, fatigue, paresthesia and pain. Our group has already demonstrated that B. henselae -infected sickle cell disease mice present with hyperalgesia. We hypothesized that even immunocompetent mice infected by B. henselae would show an increased and persistent mechanical sensitivity. Five ten-week old male BALB/c mice were intraperitoneally inoculated with a 30 µL of suspension containing 10 4 CFU/mL of B. henselae, while five others were inoculated with an equal volume of saline solution. Four days after bacterial inoculation, the mechanical paw withdrawal threshold was measured using von Frey filaments in all animals, for five consecutive days. The infected animals showed hypersensitivity to mechanical stimuli for five consecutive days. The present study has demonstrated that B. henselae infection induces persistent mechanical hypersensitivity, a signal consistent with pain.

Prevalence of Bartonella spp. Infection in Patients with Sickle Cell Disease.

Background: The inherent characteristics of the sickle cell disease (SCD), the most common genetic hematological disorder, increase the propensity of infections. Bartonella spp. are emerging and neglected bacteria. A large spectrum of clinical manifestations has been linked to bartonella bloodstream infection in the last two decades that can cause fatal outcomes, especially in immunodeficient patients. The goal of this study was to evaluate the prevalence of bartonella infection in SCD patients. Materials and Methods: We evaluated Bartonella spp. prevalence in 107 SCD patients. Blood samples and enrichment blood cultures were analyzed by molecular detection of Bartonella spp. DNA. Bartonella DNA was amplified using conventional genus-specific Bartonella PCR which amplifies the Intergenic Transcribed Spacer region and Bartonella henselae-specific nested PCR which amplifies the FtsZ gene. Positive patient DNAs were tested with ssrA conventional PCR. All amplicons were sequenced. Findings: Ten of 107 patients tested positive for B. henselae infection in at least one molecular test. All obtained amplicons were sequenced and similar to B. henselae sequences deposited in GenBank (accession number BX897699). Based on statistical results, bloodstream infection with B. henselae was not associated with animal contact or blood transfusions. Conclusion: We detected B. henselae DNA in 10 (9.3%) SCD studied patients. These patients were notified and treatment was offered to them.

Cutaneous manifestations of bartonellosis.

Bartonellosis are diseases caused by any kind of Bartonella species. The infection manifests as asymptomatic bacteremia to potentially fatal disorders. Many species are pathogenic to humans, but three are responsible for most clinical symptoms: Bartonella bacilliformis, Bartonella quintana, and Bartonella henselae. Peruvian wart, caused by B. bacilliformis, may be indistinguishable from bacillary angiomatosis caused by the other two species. Other cutaneous manifestations include maculo-papular rash in trench fever, papules or nodules in cat scratch disease, and vasculitis (often associated with endocarditis). In addition, febrile morbilliform rash, purpura, urticaria, erythema nodosum, erythema multiforme, erythema marginatus, granuloma annularis, leukocytoclastic vasculitis, granulomatous reactions, and angioproliferative reactions may occur. Considering the broad spectrum of infection and the potential complications associated with Bartonella spp., the infection should be considered by physicians more frequently among the differential diagnoses of idiopathic conditions. Health professionals and researchers often neglected this diseases.