A Case Report of Bartonella henselae Infection Causing Fever of Unknown Origin: Unveiling a Stealthy Pathogen

Bartonella species are bacterial pathogens responsible for Cat Scratch Disease (CSD) with various clinical manifestations, ranging from self-limiting febrile illnesses to severe systemic infections. Diagnosis is often challenging due to its insidious nature and variable presentation based on the body’s immune status. Such a scenario emerged when a 25-year-old male presented to our hospital with nonspecific symptoms of Fever of unknown origin that were not responding to antibiotics until a timely diagnosis of Bartonella infection. This case report highlights the importance of considering Bartonella as a potential etiology in patients with prolonged Fever of unknown origin, especially in endemic regions.

巴尔通体菌(Bartonella)

巴尔通体是一群广泛寄生在哺乳动物体内的革兰氏阴性,变形球杆菌(Pleomorphic coccobacillus),已经证实其中一些和人类疾病有关。对目前国内外巴尔通体菌的分类及一些基本特性进行了阐述。

Seronegative disseminated Bartonella spp. infection in an immunocompromised patient

An 11 year old, hispanic girl with a history of B-cell acute lymphoblastic leukemia was admitted to the hospital for symptoms compatible with Bartonella henselae infection. The first molecularly diagnosed case of disseminated Bartonella henselae infection was reported in an immunocompromised patient in Lima, Peru. The analysis was confirmed by Polymerase Chain Reaction and automated sequencing of a liver biopsy sample, even though the serologic tests were negative. In conclusion, Bartonella spp. infection should have a particular diagnostic consideration in immunocompromised patients with fever of unknown origin and further investigation regarding the patient's past exposures with cats should also be elicited.

Seroprevalence of Bartonella henselae and Identification of Risk Factors in China

Serum samples were tested for Bartonella henselae Ig G antibodies using indirect immunofluorescence assays.We then analyzed associated risk factors.Serum samples were considered positive when reactive at a dilution of more than 1:320.

Bartonella species in small mammals and their potential vectors in Asia

In this article,authors review the current knowledge of Bartonella infection in small mammals including rodents,insectivores,bats and exotic small mammal pets and their vectors in Asia.Species of Bartonella are Gram-negative intracellular bacteria that infect erythrocytes of various mammalian and non-mammalian animals and mainly transmitted by blood sucking arthropod vectors.The genus Bartonella includes several species of important human diseases with severe clinical signs.Several new Bartonella species were isolated from rodents and other small mammals,and from human patients in Asia.Bartonella species are identified using standard polymerase chain reaction amplification and a sequencing targeting two housekeeping genes(glt.A and rpoB) and the internal transcribed spacer fragment.Authors also discuss the implications in term of potential emerging zoonotic diseases.

Encephalitis with convulsive status in an immunocompetent pediatric patient caused by Bartonella henselae

Cat scratch's disease caused by Bartonella henselae, is known to be a self-limited benign process in immunocompetent children. The association with neurologic manifestations is very uncommon especially in patient with no immunologic defects and in cases without specific treatment. A 7 years old male patient, without any immunocromised defect, presented an atypic presentation of the cat scratch disease. The patient came to the hospital in two opportunities in a status epilepticus, in both cases the diagnosis was encephalitis by Bartonella henselae and the evolution with treatment was monitored with PCR(polymerase chain reaction) in cerebrospinal fluid and blood, as well as IFI(IgM, IgG) serology(indirect immunofluorescence). The patient had a favorable clinical and laboratory evolution for 6 months showing no recurrence of the disease.

Bartonella Species Investigated among Rodents from Shaanxi Province of China

Bartonella spp.are rod-shaped,Gram-negative,aerobic,fastidious,slow bacteria which cause diseases in humans and animals by parasitizing the endothelial and red blood cells of their hosts[1,2].Rodents are the most important natural reservoir hosts of Bartonella[3].In 57 countries,epidemiological studies of rat-borne Bartonella have been carried out.Information on the Bartonella infection rate in rodents has been obtained from most of these countries.The infection rate of rodents in Portugal,Egypt,Japan,Canada,and the United States is more than 90%,the infection rate in Thailand and Russia is about 80%,and the infection rate in China is about 67%.To date,22 species of rodent-borne Bartonella have been described.Of these,B.grahamii,B.vinsonii subsp.arupensis,B.vinsonii subsp.Berkhoffii,and B.elizabethae have been found to be associated with human illness.People become infected with rodent-borne Bartonella incidentally,especially when they are exposed to the habitats of wild rodents harboring various Bartonella species.Bartonella infection can affect multiple organs and poses a risk to public health[4].

Human seroreactivity against Bartonella species in the Democratic Republic of Congo

Objective:To assess the presence and identity of Bartonella species in a pool of human blood samples from DRC Congo.Methods:Blood(±120μL) was collected anonymously from Congolese patients and placed on calibrated filter papers.Bartonella serology determination was performed using an indirect immun of luorescence assay(IFA) against six specific Bartonella antigens and Coxiella burnetii(C.burnetii) antigen.The end cut- of f value for Bartonella sp.was a titre greater than 1200.Results:None of the patients was positive for Bartonella elizabethae, Bartonella vinsonii subsp.vinsonii or Bartonella vinsonii subsp.arupensis nor for C.burnetti, but 4.5%of the 1SS samples were positive for either Bartonella henselae,Bartonella quintana, or Bartonella clarridgeiae.Conclusions:This preliminary study presents the first report of Bartonella species in the DR Congo and the first report of antibodies to Bartonella clarridgeiae in an African human population.Although few experimental trials have established the link between fleas and Bartonella transmission,the repeated detection of similar Bartonella species in fleas and humans in several countries suggests that Bartonellosis could be another flea-borne disease which specific reservoirs are still unknown.

First evidence of Bartonella phoceensis and Candidatus Mycoplasma haemomuris subsp. ratti in synanthropic rodents in Malaysia

Rodent-borne leptospirosis is by far the most common bacterial zoonosis and it is an important emerging global public health concern in Southeast Asia.Bacterial pathogens associated with rodents,especially those that live in close association with humans have been underreported.To fill this knowledge gap,the present study was undertaken to explore other neglected disease agents that can naturally infect synanthropic rodents.

Bartonella infection in asymptomatic horses and donkeys from Tuscany,Central Italy

Objective: To investigate the occurrence of Bartonella sp. infection in asymptomatic horses and donkeys living in Tuscany, Central Italy.Methods: Blood samples were collected from 77 horses and 15 donkeys and tested by indirect immunofluorescent test to detect antibodies against Bartonella sp. and by PCR to detect the pathogen.Results: Fifty-four(58.69%; 95% CI: 47.95%–68.87%) animals, 9 donkeys and 45 horses, were seropositive with antibody titers ranging from 1:64 to 1:512. PCR assays detected 9 horses positive for Bartonella sp. and 3 donkeys for Bartonella henselae genotype I.Conclusions: The detected sero-prevalence suggests a common and frequent exposure of equids living in Central Italy to bartonellae and PCR results show that Bartonella sp.infection is possible both in horses and donkeys. At the best of our knowledge, this is the first report of Bartonella henselae infection in donkeys.

巴尔通体（Bartonella tribocorum）P26蛋白原核重组表达研究

目的 构建巴尔通体表面蛋白p26基因的原核重组表达载体,表达和纯化重组表达蛋白P26,并鉴定其抗原性.方法 利用PCR方法从巴尔通体B.tribocorum厦门分离株的基因组DNA中扩增出p26蛋白基因,并将该基因的编码区克隆到pGEX-4T-1表达载体中,从而构建GST-p26融合蛋白原核重组表达载体.将表达载体转化大肠埃希菌（E.coli DH5α）,诱导表达GST-p26,并运用亲和层析技术纯化蛋白.通过蛋白质斑点印迹试验和间接ELISA法检验GST-p26是否具有抗原性.结果 成功构建了p26的原核表达载体,该表达载体可在E.coli DH5α中大量表达GST-p26,原核表达的GST-p26能够与感染动物血液样本发生特异性免疫反应.结论 原核重组表达的GST-p26可作为潜在的抗原,应用于巴尔通体的血清学检测.

Optimization of Bartonella henselae multilocus sequence typing scheme using single-nucleotide polymorphism analysis of SOLID sequence data

Background Multi-locus sequence typing （MLST） is widely used to explore the population structure of numerous bacterial pathogens. However, for genotypically-restricted pathogens, the sensitivity of MLST is limited by a paucity of variation within selected loci. For Bartonella henselae （B. henselae）, although the MLST scheme currently used has been proven useful in defining the overall population structure of the species, its reliability for the accurate delineation of closely-related sequence types, between which allelic variation is usually limited to, at most, one or two nucleotide polymorphisms. Exploitation of high-throughput sequencing data allows a more informed selection of MLST loci and thus, potentially, a means of enhancing the sensitivity of the schemes they comprise. Methods We carried out SOLID resequencing on 12 representative B. henselae isolates and explored these data using single nucleotide polymorphism （SNP） analysis. We determined the number and distribution of SNPs in the genes targeted by the established MLST scheme and modified the position of loci within these genes to capture as much genetic variation as possible. Results Using genome-wide SNP data, we found the distribution of SNPs within each open reading frame （ORF） of MLST loci, which were not represented by the established B. henselae MLST scheme. We then modified the position of loci in the MLST scheme to better reflect the polymorphism in the ORF as a whole. The use of amended loci in this scheme allowed previously indistinguishable ST1 strains to be differentiated. However, the diversity of B. henselae was still rare in China. Conclusions Our study demonstrates the use of SNP analysis to facilitate the selection of MLST loci to augment the currently-described scheme for B. henselae. And the diversity among B. henselae strains in China is markedly less than that observed in B. henselae populations elsewhere in the world.

黑龙江省同江口岸首次发现花鼠携带Bartonella washoensis的分子生物学证据

目的探索黑龙江省同江口岸鼠类中可能携带Bartonella washoensis的分子生物学证据。方法 2016年6月,在黑龙江省同江口岸林缘地中,采用夹捕法和笼捕法捕获啮齿动物,采集啮齿动物脾样本,利用巴尔通体rpo B基因序列保守区引物,用PCR法检测巴尔通体,获得的阳性样本通过基因测序进一步分析。结果在捕获的113只鼠中共获得69份阳性样本,获得的序列与Gen Bank中的序列进行比对,在花鼠脾脏中获得的巴尔通体rpo B基因片段(编号:TJ2016-107)与同样是分离自花鼠的B.washoensis SR22-1株和SR25-1株同源性最高,分别为99%和98%。提示黑龙江省同江口岸花鼠中可能携带B.washoensis。结论首次在花鼠脾脏中扩增出与B.washoensis同源性较高的rpo B基因片段,这也是黑龙江省可能存在B.washoensis的直接证据。

Bartonella henselae neuroretinitis in a patient without cat scratch

Neuroretinitis is characterized by optic disc swelling with macular star,and affects 1%-2%of the patients with Bartonella henselae infection.This condition needs to be considered in the differential diagnosis of unilateral optic neuropathy in young adults.A 44-year-old woman presented with a progressive visual loss in right eye that was described as a central scotoma with altered color perception.Medical history was negative except for Hashimoto's thyroiditis.The examination evidenced a relative afferent pupillary defect in right eye and marked papillary oedema involving the macular region.Brain and orbits magnetic resonance imaging were normal,and fundoscopy showed star-shaped hard exudates.Autoimmune and infective screening revealed IgM and IgG antibodies against Bartonella henselae,suggesting for recent cat-scratch disease.She was treated with high-dose intravenous steroids and doxycycline.One month later she fully recovered,and she had no relapses.We diagnosed a Bartonella henselae neuroretinitis(finally the patient recalled she had stroked stray cats,not being scratched).In conclusion time course and absence of pain differentiate neuroretinitis from other optic neuropathies.Fundoscopic image of macular star is a clue for diagnosis,and visual recovery is usually excellent.

巴尔通体巢式PCR检测方法的建立与应用

为建立一种应用于巴尔通体(Bartonella)高灵敏度、高特异性的检测方法,根据巴尔通体16S保守序列设计特异性引物,通过优化反应体系及反应条件,建立巢式PCR检测方法,并利用该方法对在2023年广州市花都区采集的100份褐家鼠脾脏样品进行检测。结果显示:所建立的巢式PCR方法特异性良好,可特异性检测出巴尔通体阳性核酸,与其他对照菌株贝氏柯克斯体、无形体、钩端螺旋体、立克次体和伯氏螺旋体阳性核酸均无交叉反应;该方法灵敏度高,最低检出限为7.66×10^(1)copies·μL^(-1);应用该方法完成100份临床样品快速检测,检出4种巴尔通体,其中1种与人类疾病有关。表明建立的巴尔通体巢式PCR检测方法特异性强、灵敏度高,可为巴尔通体的临床样品检测提供技术支持。

Botanical Medicines With Activity Against Stationary Phase Bartonella henselae

Bartonella henselae is a Gram-negative bacterium and is the causative agent of cat scratch disease.In humans,infections with B.henselae can result in acute or chronic systemic infections with diverse clinical symptoms.The current treatment for Bartonella infections with antibiotics such as doxycycline and rifampin is not always effective,presumably due in part to bacterial persistence.There are various anecdotal reports of herbal extracts used for treating patients with persistent Bartonella infections but their activity on B.henselae is unknown.In order to identify more effective therapies for persistent Bartonella infections,in this study,we tested the antimicrobial activity of botanical and herbal medicines and screened an herbal product collection against stationary phase B.henselae in vitro using a SYBR Green I/propidium iodide viability assay.We identified five herbal product extracts(at 1.67 mg/mL or 2.5mg/mL),including Cryptolepis sanguinolenta,Juglans nigra,Polygonum cuspidatum,Scutellaria baicalensis,and Scutellaria barbata,that had high activity against stationary phase B.henselae.Among them,C.sanguinolenta,J.nigra,and P.cuspidatum could eradicate all stationary phase B.henselae cells within 7days at 0.83 mg/mL or 1.25 mg/mL in drug exposure time-kill assays,whereas S.baicalensis and S.barbata showed relatively poor activity.These top hits were active against both stationary phase nongrowing B.henselae and log phase growing B.henselae in minimum inhibitory concentration testing.These findings may have implications for improved treatment of persistent Bartonella infections.

2021—2023年东营市鼠类密度监测及病原学调查分析

目的监测东营市重点地区鼠类生态学分布、密度及携带病原体流行情况,为指导当地鼠传疾病的防控提供科学依据。方法采用夹夜法及粘鼠板法进行鼠类密度监测并捕获鼠类标本,提取组织DNA,采用实时荧光定量PCR(qPCR)开展病原体检测。用Excel 2007和SPSS 21.0软件对数据进行整理与统计分析,率的比较采用χ2检验或Fisher确切概率法。结果2021—2023年,共布放鼠夹12118个,有效夹数11741个,捕获鼠类53只,总捕鼠率为0.45%;共布放粘鼠板12271个,有效板数12066个,捕获鼠类228只,总捕鼠率为1.89%。共捕获鼠类3种281只,其中小家鼠占73.31%,褐家鼠占25.98%,黑线姬鼠占0.71%;对捕获鼠类进行病原学监测,鼠类钩端螺旋体阳性15只,巴尔通体阳性12只,分别占5.34%、4.27%;混合感染钩端螺旋体及巴尔通体阳性3只,复合感染率为1.07%。结论东营市优势鼠种为小家鼠,病原学监测阳性以钩端螺旋体为主,且呈逐年上升趋势,应进一步扩大鼠类监测覆盖面,增强病原学监测力度。

Cat scratch disease in children with nocturnal fever:A case report

BACKGROUND Cat scratch disease(CSD)is the most common human infection caused by Barto-nella henselae(B.henselae).The main manifestation is self-limited lymphaden-opathy that primarily affects adolescents,and typically resolves without treat-ment within 2-4 months.However,individuals with compromised immune systems or immunodeficiency require specific antibacterial therapy following diagnosis.Due to its low incidence,nonspecific clinical manifestations,and diagnostic limitations,this condition often poses challenges for clinicians in terms of missed diagnoses and misdiagnoses.CASE SUMMARY The child was ultimately diagnosed with CSD.The primary manifestations included nocturnal fever,enlargement of lymph nodes in the neck,axilla and groin,and suspected brucellosis;however,both brucellosis tests conducted during the course of the illness yielded negative results.Bone marrow cytology indicated stimulated proliferation.Lymph node biopsy indicated hyperplasia of lymphoid tissue in the cervical lymph nodes(right),with combined immunohisto-chemical findings indicating reactive hyperplasia.Immunohistochemical analysis revealed CD20 B(+),CD3 T(+),BCL-6(+),and BCL-2(-).CD21 FDC networks were present and Ki67 expression in the germinal center was~80%.Blood next-generation sequencing indicated B.henselae sequence number was 3.Serological test results demonstrated positive antibody response to B.henselae IgG(+),B.henselae IgM(+),Bartonella quintana(B.quintana)IgG(-)and B.quintana IgM(-),and the final diagnosis was CSD.CONCLUSION In patients presenting with fever at night and swollen lymph nodes of unknown origin,CSD should be considered.

2022—2023年内蒙古自治区部分地区啮齿动物携带巴尔通体的调查分析

目的调查内蒙古自治区啮齿动物巴尔通体(Bartonella)感染及型别分布情况,分析其带毒率。方法2022—2023年在内蒙古自治区呼和浩特市、包头市、呼伦贝尔市、兴安盟、通辽市、赤峰市、锡林郭勒盟、乌兰察布市、鄂尔多斯市和巴彦淖尔10盟市采集啮齿动物肝、脾、肾组织样本,应用TaqMan探针荧光定量PCR(qPCR)法检测巴尔通体病原,对qPCR检测阳性的标本再进行PCR扩增,阳性结果进行测序和遗传进化分析。结果此次调查捕获啮齿动物799只,其中小家鼠271只(33.92%,271/799),褐家鼠188只(23.53%,188/799),长爪沙鼠188只(23.53%,188/799)。组织检测结果显示,qPCR阳性49份,阳性率6.13%(49/799),PCR阳性29份。序列与遗传进化分析表明内蒙古地区啮齿动物巴尔通体分别检出B.krasnovii(55.17%,16/29)、未命名巴尔通体(34.48%,10/29)、B.tribocorum(6.90%,2/29)和B.rochalimae(3.45%,1/29)4种巴尔通体。结论内蒙古地区多个盟市啮齿动物巴尔通体普遍感染,存在巴尔通体基因型别的多样性和宿主多样性特征。应加强啮齿动物携带病原体的监测,优化鼠传疾病的防治工作,降低人群感染风险。

2021—2023年青岛市小兽携带鼠传病原体监测分析

目的调查青岛市小兽携带病原体基本情况,为鼠传疾病的防控工作提供理论依据。方法2021—2023年在青岛市西海岸新区、即墨区、胶州市、平度市和莱西市采集小兽肝、脾、肾和肺组织的核酸样本,采用实时荧光定量PCR(Quantitative Real-time PCR,qPCR)检测致病性钩端螺旋体和巴尔通体,反转录实时荧光定量PCR(Reverse transcription-qPCR,RT-qPCR)方法检测汉坦病毒和新型布尼亚病毒。对种群构成比、病原体感染率进行统计学分析。结果本次共捕获小兽624只,其中褐家鼠最多,占比为4311%,小家鼠占比为3686%、黑线姬鼠占比为1394%、鼩鼱占比为609%。病原学检测结果显示,鼠传病原体中汉坦病毒感染率为337%,致病性钩端螺旋体感染率为096%,巴尔通体感染率为112%;未检出新型布尼亚病毒。褐家鼠和小家鼠均检出3种病原体,以褐家鼠携带病原体感染率最高;监测生境中农田耕地生境鼠病原体检出感染率最高为820%。结论青岛市存在汉坦病毒、巴尔通体、致病性钩端螺旋体的鼠传病原感染情况,应加强农村地区的鼠传病原体监测和防控工作,降低人群鼠传病原体的感染风险。