Genomic properties of a Bartonella quintana strain from Japanese macaque (Macaca fuscata) revealed by genome comparison with human and rhesus macaque strains.

Bartonella quintana, the causative agent of trench fever, is an intracellular bacterium that infects human erythrocytes and vascular endothelial cells. For many years, humans were considered the only natural hosts for B. quintana; however, it was recently discovered that wild Japanese macaques (Macaca fuscata) also serve as hosts for B. quintana. To elucidate the genetic characteristics of the B. quintana strain MF1-1 isolated from a Japanese macaque, we determined the complete genome sequence of the strain and compared it with those of strain Toulouse from a human and strain RM-11 from a rhesus macaque. General genomic features and orthologous gene cluster profiles are similar among the three strains, and strain MF1-1 is genetically closer to strain RM-11 than strain Toulouse based on the average nucleotide identity values; however, a significant inversion of approximately 0.68 Mb was detected in the chromosome of strain MF1-1. Moreover, the Japanese macaque strains lacked the bepA gene, which is responsible for anti-apoptotic function, and the trwL2, trwL4, and trwL6 genes, which may be involved in adhesion to erythrocytes of rhesus macaque and human. These features likely represent the genomic traits acquired by Japanese macaque strains in their host-associated evolution.

In silico identification of drug targets and vaccine candidates against Bartonella quintana: a subtractive proteomics approach.

BACKGROUND: The availability of genes and protein sequences for parasites has provided valuable information for drug target identification and vaccine development. One such parasite is Bartonella quintana, a Gram-negative, intracellular pathogen that causes bartonellosis in mammalian hosts. OBJECTIVE: Despite progress in understanding its pathogenesis, limited knowledge exists about the virulence factors and regulatory mechanisms specific to B. quintana. METHODS AND FINDINGS: To explore these aspects, we have adopted a subtractive proteomics approach to analyse the proteome of B. quintana. By subtractive proteins between the host and parasite proteome, a set of proteins that are likely unique to the parasite but absent in the host were identified. This analysis revealed that out of the 1197 protein sequences of the parasite, 660 proteins are non-homologous to the human host. Further analysis using the Database of Essential Genes predicted 159 essential proteins, with 28 of these being unique to the pathogen and predicted as potential putative targets. Subcellular localisation of the predicted targets revealed 13 cytoplasmic, eight membranes, one periplasmic, and multiple location proteins. The three-dimensional structure and B cell epitopes of the six membrane antigenic protein were predicted. Four B cell epitopes in KdtA and mraY proteins, three in lpxB and BQ09550, whereas the ftsl and yidC proteins were located with eleven and six B cell epitopes, respectively. MAINS CONCLUSIONS: This insight prioritises such proteins as novel putative targets for further investigations on their potential as drug and vaccine candidates.

Genomic detection and phylogenetic analysis of Bartonella quintana in pet cats from Urmia City, Northwest Iran.

The aim of this study was to investigate the presence and genetic characteristics of Bartonella quintana in pet cats from Urmia City, located in the northwest of Iran. Blood samples were collected from 200 cats, and their age, gender, and breed were noted. Nested-PCR and sequencing were used to identify B. quintana in positive samples, and the ftsZ gene sequences were analyzed using BioEdit software. The gene sequence obtained in this study exhibited 100.00 % similarity to reference sequences in the GenBank® database, and a phylogenetic tree was constructed using MEGA11. The results revealed that 15 % of the cats (30 out of 200 blood samples) tested positive for the B. quintana gene, with a 95 % confidence interval of 10.71 % to 20.61 %.

An autochthonous case of cutaneous bacillary angiomatosis not related to major immunosuppression: An emerging or overlooked disease?

Cutaneous bacillary angiomatosis (cBA) is a vascular proliferative disorder due to Bartonella henselae or Bartonella quintana that has been mostly described in people living with HIV. Since cBA is considered to be rare in hosts not affected by major immunosuppression, it could be underdiagnosed in this population. Moreover, antimicrobial treatment of cBA has been poorly validated, thus reporting experiences on this clinical entity is important. We reported a challenging and well-characterized case of an Italian 67-year-old gentleman without a history of major immunocompromizing conditions, although he was affected by conditions that can be associated with impaired immune function. The patient reported herein was diagnosed after a long time since the initiation of symptoms and was successfully treated with combined antibiotic therapy including macrolides and quinolones under the guidance of molecular test results. Physicians should consider cBA as a possible manifestation of Bartonella spp. Infection in patients not suffering from major immunocompromizing conditions. Until evidence-based guidelines are available, molecular tests together with severity and extension of the disease can be useful to personalize the type of treatment and its duration.

Bartonella quintana Endocarditis: A Systematic Review of Individual Cases.

BACKGROUND: Bartonella quintana is a louse-borne bacterium that remains a neglected cause of endocarditis in low-resource settings. Our understanding of risk factors, clinical manifestations, and treatment of B. quintana endocarditis are biased by older studies from high-income countries. METHODS: We searched Pubmed Central, Medline, Scopus, Embase, EBSCO (CABI) Global Health, Web of Science and international trial registers for articles published before March 2023 with terms related to Bartonella quintana endocarditis. We included articles containing case-level information on B. quintana endocarditis and extracted data related to patient demographics, clinical features, diagnostic testing, treatment, and outcome. RESULTS: A total of 975 records were identified, of which 569 duplicates were removed prior to screening. In total, 84 articles were eligible for inclusion, describing a total of 167 cases. Infections were acquired in 40 different countries; 62 cases (37.1%) were acquired in low- and middle-income countries (LMICs). Disproportionately more female and pediatric patients were from LMICs. More patients presented with heart failure (n = 70/167 [41.9%]) than fever (n = 65/167 [38.9%]). Mean time from symptom onset to presentation was 5.1 months. Also, 25.7% of cases (n = 43/167) were associated with embolization, most commonly to the spleen and brain; 65.5% of antimicrobial regimens included doxycycline. The vast majority of cases underwent valve replacement surgery (n = 154/167, [98.0%]). Overall case fatality rate was 9.6% (n = 16/167). CONCLUSIONS: B. quintana endocarditis has a global distribution, and long delays between symptom onset and presentation frequently occur. Improved clinician education and diagnostic capacity are needed to screen at-risk populations and identify infection before endocarditis develops.

Molecular detection of Bartonella quintana, Acinetobacter baumannii and Acinetobacter haemolyticus in Pediculus humanus lice in Nigeria, West Africa.

The human lice Pediculus humanus is distributed worldwide but, it thrives and flourishes under conflict situations where people are forced to live in crowded unhygienic conditions. Molecular methods were used to identify and screen human lice for the DNA of pathogens of public health importance in an area that has been under insurgency related to religious and political conflicts with tens of thousands of internally displaced people (IDP). DNA of Bartonella quintana, Acinetobacter baumannii and Acinetobacter haemolyticus was detected in 18.3%, 40.0% and 1.7%, respectively, of human lice collected from children in Maiduguri, Nigeria. More body lice than head lice were positive for pathogen's DNA (64.3% vs. 44.4%; χ2 = 1.3, p = 0.33), but the difference was not significant. Two lice samples were found to harbour mixed DNA of B. quintana and A. baumannii. Phylogenetic analysis of the cytochrome b (cytb) gene sequences of the positive lice specimens placed them into clades A and E. This is the first report on the molecular identification of human lice and the detection of the DNA of pathogens of public health importance in lice in Nigeria, West Africa. The findings of this study will assist policy makers and medical practitioners in formulating a holistic healthcare delivery to IDPs.

The Silent Threat: Bartonella quintana Endocarditis Unveiling Heart Failure and Severe Pulmonary Hypertension.

BACKGROUND Bartonella quintana is a slow-growing gram-negative bacterium that can cause severe culture-negative endocarditis. In many cases, its insidious onset can be difficult to diagnose given the variable symptoms in the early phases of the disease. This delay in detection and thus treatment can cause advanced consequences of the disease, including heart failure and severe pulmonary hypertension. CASE REPORT A 51-year-old man presented to the Emergency Department with signs and symptoms indicating an acute stroke. Further investigation showed that the source was cardioembolic, and despite negative blood cultures, endocarditis was suspected due to echocardiogram findings. Bartonella endocarditis was diagnosed based on serology results. Further testing indicated severe pulmonary hypertension, a sequelae of chronic heart failure in the setting of endocarditis. This caused a significant delay in valvular repair surgery. This case illustrates the progression from acute to chronic infection, the sequelae of this disease process, and the considerations involved in management. CONCLUSIONS Bartonella is an under-appreciated cause of endocarditis and can evolve into chronic disease with clinical consequences requiring nuanced management. We described a case of chronic culture-negative endocarditis that presented with acute embolic stroke and the sequelae of severe multi-valvular disease in a patient with recent incarceration and unstable housing. This case provides clinicians with valuable insight into the recognition of Bartonella endocarditis, the variable clinical presentations of this pathology, the nuanced and multifactorial approaches to medical management, and the indications for surgery.

POPULATION STRUCTURE AND BARTONELLA QUINTANA IN HEAD AND BODY LICE IN POKHARA, NEPAL (ANOPLURA: PEDICULIDAE).

This study examined the population structure of head and body lice infesting a random sample of people in Pokhara, Nepal during 2003, 2004, and 2005. A total of 106 participants (6 to 72 yr old, median = 12) volunteered to have lice collected from their heads and clothing. Most participants (70%) harbored only head lice, some (15%) had only body lice, and some (15%) had concurrent infestations of head and body lice (dual infestations). A total of 1,472 lice was collected. Significantly more nymphs were collected than adult lice. Louse populations were generally small (geometric mean = 8.8 lice per person) but a few participants harbored larger louse populations (maximum = 65 lice). People with dual infestations harbored significantly more lice than people with single infestations; however, there was no difference in the infestation intensities between people infested with head lice only vs. those infested with body lice only. Male participants harbored significantly more lice than did females. There were no significant differences in infestation intensity due to participant age or their socioeconomic level. The sex ratio of adult lice was increasingly female biased with increasing adult louse density. Infection of lice with Bartonella quintana was low (ca. 1.5%). Pediculosis is a common problem in urban Nepal.

Case series of 12 Bartonella quintana endocarditis from the Southwest Indian Ocean.

BACKGROUND: Bartonella spp. are fastidious bacteria frequently identified as the cause of blood culture-negative (BCN) endocarditis. However, Bartonella infections are difficult to diagnose in routine laboratory testing and their incidence is probably underestimated. We investigated the epidemiological and clinical features of Bartonella endocarditis cases diagnosed between 2009 and 2021 on Reunion Island (Southwest Indian Ocean). METHOD: We retrospectively included all patients diagnosed with Bartonella endocarditis at Reunion Island University Hospital during this period. Endocarditis was diagnosed on the basis of microbiological findings, including serological tests (IFA) and PCR on cardiac valves, and the modified Duke criteria. We used then the multispacer typing (MST) method to genotype the available Bartonella strains. FINDINGS: We report 12 cases of B. quintana endocarditis on Reunion Island (83.3% in men, median patient age: 32 years). All the patients originated from the Comoros archipelago. The traditional risk factors for B. quintana infection (homelessness, alcoholism, exposure to body lice) were absent in all but two of the patients, who reported head louse infestations in childhood. Previous heart disease leading to valve dysfunction was recorded in 50% of patients. All patients underwent cardiac valve surgery and antimicrobial therapy with a regimen including doxycycline. All patients presented high C-reactive protein concentrations, anemia and negative blood cultures. The titer of IgG antibodies against Bartonella sp. exceeded 1:800 in 42% of patients. Specific PCR on cardiac valves confirmed the diagnosis of B. quintana endocarditis in all patients. Genotyping by the MST method was performed on four strains detected in preserved excised valves and was contributive for three, which displayed the MST6 genotype. CONCLUSIONS: Bartonella quintana is an important cause of infective endocarditis in the Comoros archipelago and should be suspected in patients with mitral valve dysfunction and BCN from this area.

Exploring the potential role of defensins in differential vector competence of body and head lice for Bartonella quintana.

BACKGROUND: The body and head lice of humans are conspecific, but only the body louse functions as a vector to transmit bacterial pathogens such as Bartonella quintana. Both louse subspecies have only two antimicrobial peptides, defensin 1 and defensin 2. Consequently, any differences in the molecular and functional properties of these two louse subspecies may be responsible for the differential vector competence between them. METHODS: To elucidate the molecular basis of vector competence, we compared differences in the structural properties and transcription factor/microRNA binding sites of the two defensins in body and head lice. Antimicrobial activity spectra were also investigated using recombinant louse defensins expressed via baculovirus. RESULTS: The full-length amino acid sequences of defensin 1 were identical in both subspecies, whereas the two amino acid residues in defensin 2 were different between the two subspecies. Recombinant louse defensins showed antimicrobial activities only against the representative Gram-positive Staphylococcus aureus but not against either Gram-negative Escherichia coli or the yeast Candida albicans. However, they did show considerable activity against B. quintana, with body louse defensin 2 being significantly less potent than head louse defensin 2. Regulatory sequence analysis revealed that the gene units of both defensin 1 and defensin 2 in body lice possess decreased numbers of transcription factor-binding sites but increased numbers of microRNA binding sites, suggesting relatively lower transcription activities of body louse defensins. CONCLUSIONS: The significantly lower antibacterial activities of defensin 2 along with the reduced probability of defensin expression in body lice likely contribute to the relaxed immune response to B. quintana proliferation and viability, resulting in higher vector competence of body lice compared to head lice.

Development and validation of a real-time PCR test to detect Bartonella quintana in clinical samples.

This study reports on the validation of a real-time polymerase chain reaction test targeting the vomp region of Bartonella quintana. The assay displayed 100% sensitivity and specificity for the 52 bloods and 159 cultures tested. Molecular diagnosis of Bartonella quintana can aid clinical treatment during acute infection.

Molecular epidemiology of Bartonella quintana endocarditis in patients from Israel and Eastern Africa.

BACKGROUND: Bartonella quintana is an important cause of culture-negative endocarditis. Although humans have been considered as its only reservoir, recent studies showed that macaque species are also reservoirs of B. quintana. Based on multi-locus sequence typing (MLST) B. quintana strains have been classified into 22 sequence types (STs), with 7 STs exclusively found in humans. Data regarding the molecular epidemiology of B. quintana endocarditis is limited to only 3 STs identified in 4 patients from Europe and Australia. We studied B. quintana endocarditis acquired in Eastern Africa or Israel to investigate the genetic diversity and clinical relatedness of B. quintana from distinct geographic regions. METHODS: Eleven patients with B. quintana endocarditis, 6 from Eastern Africa and 5 from Israel, were studied. DNA was extracted from cardiac tissue or blood specimens and analyzed by MLST based on 9 genetic loci. An evolutionary relationship between STs was visualized by a minimum spanning tree. A phylogenetic tree was constructed with the concatenated sequences (4271 bp) of the 9 loci using the maximum-likelihood method. RESULTS: Six strains were classified into previously described STs while 5 strains were identified for the first time and classified into new STs 23-27 which clustered with the previously reported STs 1-7 from human strains found in Australia, France, Germany, the USA, Russia, and the former Yugoslavia, without indication of geographical structuring. ST2 was the most prevalent ST, found in 5 of 15 patients with endocarditis (33.3%). ST26 appears to be a primary founder of the human lineage. CONCLUSIONS: The new and previously reported human STs form a single human lineage, clearly separated from the other 3 B. quintana lineages of cynomolgus, rhesus, and Japanese macaques. From evolutionary perspectives, these findings support the assumption that B. quintana has co-evolved with host species to form a host-speciation pattern. ST26 is suggested herein as a primary founder of the human lineage and may be key to explore where B. quintana had first originated; ST2 is a dominant genetic type associated with B. quintana endocarditis. To confirm these findings, additional worldwide molecular epidemiological studies are required.

Detection of Bartonella quintana (Hyphomicrobiales: Bartonellaceae) Among Day Laborers in Osaka, Japan, 2009-2010.

Bartonella quintana is a gram-negative bacterium causing trench fever, an illness historically acquired by soldiers during World War I. More recently, outbreaks of trench fever have been reported in those experiencing homelessness in the United States, France, Russia, and Tokyo, as well as in children in Nepal and persons in Ethiopia. Reports of B. quintana infection outside of Tokyo are rare in Japan. The aim of this study was to examine body lice and blood obtained from people staying in shelters in Osaka (2009-2010) for B. quintana via polymerase chain reaction and enzyme-linked immunosorbent assays. Day laborers were defined as homeless individuals and shelter residents in this study. We detected genes of B. quintana in body lice by PCR and antibodies against B. quintana. The positive rate of B. quintana genes was 6/10 (60%) in body lice and the seroprevalence (IgG) of B. quintana was 4/10 (40%). This demonstrates that trench fever was endemic in people staying in shelters in Osaka in 2009-2010.

Bartonella quintana Transmitted by Head Lice: An Outbreak of Trench Fever in Senegal.

BACKGROUND: Louse-borne trench fever caused by Bartonella quintana is a neglected public health concern, known to be transmitted from body louse feces via scratching. No viable B. quintana have ever been isolated from head lice before; therefore, their role as a vector is still poorly understood. METHODS: In Senegal, the implementation of a permanent local surveillance system in a point-of-care laboratory (POC) allows the monitoring of emerging diseases. Here we used culture as well as molecular and genomic approaches to document an outbreak of trench fever associated with head lice in the village of Ndiop. Head lice and blood samples were collected from febrile patients between November 2010 and April 2015. Genomes of 2 isolated strains of B. quintana were sequenced and analyzed. RESULTS: A total of 2289 blood samples were collected in the 2010-2015 period. From 2010-2013, B. quintana DNA was detected by polymerase chain reaction (PCR) in 0.25% (4/1580). In 2014, 228 blood samples were collected, along with 161 head lice from 5 individuals. B. quintana DNA was detected in 4.4% (10/228) of blood samples, and in lice specimens collected from febrile patients (61.7%, 50/81) and non-febrile patients (61.4%, 43/70). Two B. quintana strains were isolated from blood and head lice from 2 different patients. Genomic sequence analysis showed 99.98% overall similarity between both strains. CONCLUSIONS: The presence of live B. quintana in head lice, and the genetic identity of strains from patients' blood and head lice during a localized outbreak in Senegal, supports the evidence of head lice vectorial capacity.

Autoimmune Thyroiditis Induced by Bartonella henselae (Cat-Scratch Disease) Might Be Reversible.

INTRODUCTION: Bartonella henselae infection leads to development of cat-scratch disease (CSD) but may also trigger of autoimmune thyroiditis (AIT). CASE PRESENTATION: We describe a 4-year-old boy with a severe fever of unknown etiology, disseminated neck lymphadenopathy, and a headache. Treatment with antibiotics was employed, but finally a left tonsillectomy, selective left lymphadenectomy, and immunophenotyping were performed to exclude lymphoma. Histologic examination excluded lymphoma but revealed CSD. IgG against B. henselae and Bartonella quintana was positive. A goiter was also found and positive anti-thyroid antibodies confirmed AIT. Two months later, the thyroid was not palpable, normal on ultrasound, and both anti-thyroid antibodies were negative. The full reversibility was documented, and 6-year follow-up showed that the patient remains disease free. CONCLUSION: This is the first report that AIT triggered by B. henselae/B. qunitana might be reversible if the pathogenetic factor is eliminated at an early stage of disease.

Examination of vertical transmission of Bartonella quintana in body lice following multiple infectious blood meals.

Bartonella quintana is a re-emerging louse-borne pathogen. Horizontal transmission from the body louse vector (Pediculus humanus humanus) to a human host occurs through contact with infectious louse feces containing a high concentration of the bacteria. However, questions have remained about whether vertical transmission from infected vectors to their progeny, which could significantly influence the dynamics of transmission to humans, occurs in body lice. To address this subject, we performed a series of controlled laboratory experiments that examined the presence of B. quintana on the surface of and within eggs produced by female body lice that were provisioned multiple infectious blood meals to recapitulate the natural pathogen acquisition process. Our results demonstrate that B. quintana DNA can be detected from the surface of eggs by qPCR due to vertical transfer of infectious feces to the egg sheath during or after oviposition. However, viable B. quintana could not be cultured from the hemolymph of adult female lice or from within eggs that were surface sterilized, indicating a lack of true transovarial transmission. Based on this evidence, vertical transfer of B. quintana from infected adult lice to their eggs probably has a limited impact on the dynamics of transmission to humans.

Body Lice among People Experiencing Homelessness and Access to Hygiene Services during the COVID-19 Pandemic-Preventing Trench Fever in Denver, Colorado, 2020.

Eight people with human body louse-borne Bartonella quintana infections were detected among people experiencing homelessness (PEH) in Denver during January-September 2020, prompting a public health investigation and community outreach. Public health officials conducted in-person interviews with PEH to more fully quantify body lice prevalence, transmission risk factors, access to PEH resources, and how the COVID-19 pandemic has affected resource access. Recent body lice exposure was reported by 35% of 153 interview participants. In total, 75% of participants reported reduced access to PEH services, including essential hygiene activities to prevent body lice, during Colorado's COVID-19 stay-at-home orders. Future pandemic planning should consider hygiene resource allocation for PEH populations to prevent emerging and reemerging infections such as B. quintana.

Hundreds of vasculoproliferative skin lesions in a paediatric renal transplant recipient.

Bacillary angiomatosis is a vasculoproliferative infectious disease mostly recorded in patients with human immunodeficiency virus and rarely in organ transplant recipients. We report the first case of bacillary angiomatosis due to Bartonella quintana in a paediatric renal transplant patient with skin, lymph node and bone involvement with excellent response to doxycycline. Click here for the corresponding questions to this CME article.

Bartonella quintana Infection in People Experiencing Homelessness in the Denver Metropolitan Area.

BACKGROUND: Bartonella quintana is an important cause of infection amongst people experiencing homelessness that is underdiagnosed due to its nonspecific clinical manifestations. We reviewed cases identified in the Denver metropolitan area in 2016-2021. METHODS: The electronic medical records from 2 large academic medical centers in Colorado were reviewed for demographic, clinical, and laboratory features of patients with B. quintana infection confirmed by blood culture, serologies, and/or molecular testing from July 2016 to December 2021. RESULTS: Fourteen patients with B. quintana infection were identified. The mean age was 49.5 years (SD 12.7 years) and 92.9% of patients were male. Twelve patients had history of homelessness (85.7%) and 11 were experiencing homelessness at the time of diagnosis (78.6%). Most frequent comorbidities included substance use (78.6%), of which 42.9% had alcohol use disorder. The average time to blood culture positivity was 12.1 days (SD 6.2 days). Three patients with bacteremia had negative B. quintana IgG, and 6 of 14 (42.8%) patients had evidence of endocarditis on echocardiography. CONCLUSIONS: B. quintana is an underrecognized cause of serious infection in individuals experiencing homelessness. Serologic and microbiologic testing, including prolonged culture incubation, should be considered in at-risk patients due to ongoing transmission in homeless populations.