DOCSLIB.ORG

Genotyping and Genomotyping of Tropheryma Whipplei – the Causative Agent of Whipple's Disease»

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Genotyping and Genomotyping of Tropheryma Whipplei – the Causative Agent of Whipple's Disease» Aus der Klinik für Innere Medizin der Medizinischen Fakultät Charité – Universitätsmedizin Berlin und der Unité de recherche sur les Maladies infectieuses et tropicales émergentes Marseille DISSERTATION «Genotyping and Genomotyping of Tropheryma whipplei – The Causative Agent of Whipple's Disease» zur Erlangung des akademischen Grades Doctor medicinae (Dr. med.) vorgelegt der Medizinischen Fakultät Charité – Universitätsmedizin Berlin von Nils Wetzstein aus Hanau Datum der Promotion: 08.12.2017 1 Table of Contents 1. Abstracts.................................................................................................................................................7 1.1. Abstract...........................................................................................................................................7 1.2. Zusammenfassung..........................................................................................................................7 2. Introduction...........................................................................................................................................9 2.1. Historical introduction....................................................................................................................9 2.2. Epidemiology and transmission......................................................................................................9 2.3. Clinical manifestations.................................................................................................................10 2.4. Antibiotic treatment......................................................................................................................12 2.5. Diagnostics...................................................................................................................................12 2.6. Bacteriology and phylogeny.........................................................................................................13 2.7. Bacterial typing systems...............................................................................................................14 2.8. Geographical distribution and disease outcome............................................................................14 2.9. Bacterial genomics and application in TW...................................................................................15 2.10. Bacterial core and pan-genomes.................................................................................................15 2.11. Problems addressed in this study................................................................................................16 3. Materials & Methods...........................................................................................................................17 3.1. Utilized reagents and devices........................................................................................................17 3.2. Strains of TW................................................................................................................................19 3.3. Axenic culture of TW...................................................................................................................19 3.4. Harvesting....................................................................................................................................19 3.5. Verification of purity on cellular level..........................................................................................20 3.5.1. Classical staining methods...................................................................................................21 3.5.2. Immunofluorescence...........................................................................................................21 3.6. DNA-extraction............................................................................................................................21 3.7. Verification of purity on the DNA-level.......................................................................................22 3.8. Genotyping based on HVGS-regions............................................................................................23 2 3.9. Epidemiological, phylogenetic and geographical analysis of typing data.....................................25 3.10. Basic genomic data and sequencing............................................................................................26 3.11. Genomic analysis........................................................................................................................26 3.12. Geographic distribution of sequenced genomes..........................................................................27 3.13. Calculation of core and pan-genome...........................................................................................28 4. Results...................................................................................................................................................29 4.1. Patients' characteristics and clinics...............................................................................................29 4.2. Genotyping of remaining strains...................................................................................................29 4.3. Analysis of genotyping data in patient group including prior genotyping results..........................30 4.4. Sequenced genomes, genome length and GC-content...................................................................32 4.5. Geographic distribution of sequenced genomes and ANI distance matrix....................................32 4.6. Phylogenetic analysis of sequenced strains using genotyping data...............................................35 4.7. Phylogenetic analysis of sequenced strains using whole-genomes...............................................35 4.8. ANI-comparison of most important genotypes and different clinical entities...............................36 4.10. Comparison of TW with other intracellular pathogenic bacteria and other species in the group of Actinobacteria......................................................................................................................................37 4.11. Comparison of RAST annotation in TW strains..........................................................................39 4.12. Prediction of antibiotic resistance genes and phage DNA...........................................................39 4.13. Core-genome and pan-genome...................................................................................................40 4.14. WiSPs in the core and pan-genome.............................................................................................41 5. Discussion.............................................................................................................................................43 5.1. Patients' characteristics and clinics...............................................................................................43 5.2. Analysis of genotyping data..........................................................................................................43 5.3. Sequenced genomes, genome length and GC-content...................................................................44 5.4. Geographic distribution of sequenced genomes............................................................................45 5.5. Phylogenetic analysis of sequenced strains...................................................................................46 5.6. Core and pan-genome...................................................................................................................46 5.7. Host and pathogen factors in WD.................................................................................................47 3 5.8. Prediction of antibiotic resistance genes: fluoroquinolone resistance gene...................................48 5.9. Limitations of this study...............................................................................................................48 5.10. Conclusion..................................................................................................................................48 6. Bibliography.........................................................................................................................................50 7. Eidesstattliche Erklärung....................................................................................................................55 8. Anteilserklärung an erfolgten Publikationen.....................................................................................56 9. Curriculum Vitae.................................................................................................................................57 10. Acknowledgments..............................................................................................................................58 4 Abbreviations AC asymptomatic carriers / asymptomatic carriage ANI average nucleotide identity APHM Assistance Publique – Hôpitaux de Marseille BCYE-Agar buffered charcoal yeast extract agar BDBH bidirectional best hit algorithm BLAST basic local alignment search tool CDC Centers for Disease Control and Prevention COG cluster of orthologous groups COS-Agar Columbia agar with 5% sheep blood CSF cerebrospinal fluid CWD classical Whipple’s disease DMEM F12 Dulbecco's modified Eagle medium F12 DNA deoxyribonucleic acid NW neurological manifestations due to Whipple's
Load more

Recommended publications
  • Pdfs/ Ommended That Initial Cultures Focus on Common Pathogens, Pscmanual/9Pscssicurrent.Pdf)
    Clinical Infectious Diseases IDSA GUIDELINE A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiologya J. Michael Miller,1 Matthew J. Binnicker,2 Sheldon Campbell,3 Karen C. Carroll,4 Kimberle C. Chapin,5 Peter H. Gilligan,6 Mark D. Gonzalez,7 Robert C. Jerris,7 Sue C. Kehl,8 Robin Patel,2 Bobbi S. Pritt,2 Sandra S. Richter,9 Barbara Robinson-Dunn,10 Joseph D. Schwartzman,11 James W. Snyder,12 Sam Telford III,13 Elitza S. Theel,2 Richard B. Thomson Jr,14 Melvin P. Weinstein,15 and Joseph D. Yao2 1Microbiology Technical Services, LLC, Dunwoody, Georgia; 2Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; 3Yale University School of Medicine, New Haven, Connecticut; 4Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland; 5Department of Pathology, Rhode Island Hospital, Providence; 6Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill; 7Department of Pathology, Children’s Healthcare of Atlanta, Georgia; 8Medical College of Wisconsin, Milwaukee; 9Department of Laboratory Medicine, Cleveland Clinic, Ohio; 10Department of Pathology and Laboratory Medicine, Beaumont Health, Royal Oak, Michigan; 11Dartmouth- Hitchcock Medical Center, Lebanon, New Hampshire; 12Department of Pathology and Laboratory Medicine, University of Louisville, Kentucky; 13Department of Infectious Disease and Global Health, Tufts University, North Grafton, Massachusetts; 14Department of Pathology and Laboratory Medicine, NorthShore University HealthSystem, Evanston, Illinois; and 15Departments of Medicine and Pathology & Laboratory Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey Contents Introduction and Executive Summary I.
    [Show full text]
  • A Phylogenetic Approach in Actinobacteria
    On the nature of fur evolution: A phylogenetic approach in Actinobacteria Catarina L Santos, João Vieira, Fernando Tavares, David R Benson, Louis S Tisa, Alison M Berry, Pedro Moradas-Ferreira, Philippe Normand To cite this version: Catarina L Santos, João Vieira, Fernando Tavares, David R Benson, Louis S Tisa, et al.. On the nature of fur evolution: A phylogenetic approach in Actinobacteria. BMC Evolutionary Biology, BioMed Central, 2008, 8 (185), pp.1-14. 10.1186/1471-2148-8-185. halsde-00354531 HAL Id: halsde-00354531 https://hal.archives-ouvertes.fr/halsde-00354531 Submitted on 30 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. BMC Evolutionary Biology BioMed Central Research article Open Access On the nature of fur evolution: A phylogenetic approach in Actinobacteria Catarina L Santos*1,2, João Vieira1, Fernando Tavares1,2, David R Benson3, Louis S Tisa4, Alison M Berry5, Pedro Moradas-Ferreira1,6 and Philippe Normand7 Address: 1IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal, 2Faculdade de Ciências da Universidade do Porto, Departamento de Botânica, Rua do Campo Alegre 1191, 4150-181 Porto, Portugal, 3Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06279, USA, 4Department of Microbiology, University of New Hampshire, Durham, NH, 03824, USA, 5Department of Plant Sciences, Mail Stop 1, PES Building, University of California, Davis, CA 95616, USA, 6Instituto de Ciências Biomédicas Abel Salazar, Lg.
    [Show full text]
  • Tropheryma Whipplei Was 44%
    DISPATCHES (mean 3.5 years ± 2.5 years) living in 2 villages in Senegal Tropheryma (Ndiop, 77 children; Dielmo, 73 children) (6). These vil- lages are included in the Dielmo project, initiated in 1990 whipplei in Fecal for long-term investigations of host–parasite associations in the entire village population, which was enrolled in a Samples from longitudinal prospective study (6,7). At the beginning of Children, Senegal the current study, parents or legal guardians of all children gave individual informed consent. The national ethics com- Florence Fenollar, Jean-François Trape, mittee of Senegal approved the project (6). Eight wells in Hubert Bassene, Cheikh Sokhna, the 2 villages (5 from Dielmo, 3 from Ndiop), which are the and Didier Raoult only sources of drinking water for the communities, also were sampled. We tested fecal samples from 150 healthy children After collection, each fecal specimen was mixed with 2–10 years of age who lived in rural Senegal and found the 2.5 mL of absolute ethanol for storage and transportation prevalence of Tropheryma whipplei was 44%. Unique geno- to our laboratory at room temperature. On arrival, DNA types were associated with this bacterium. Our findings was extracted by using the BioRobot MDx workstation suggest that T. whipplei is emerging as a highly prevalent pathogen in sub-Saharan Africa. (QIAGEN, Valencia, CA, USA) in accordance with the manufacturer’s recommendations and protocols. T. whip- plei quantitative PCR assays were performed as previously ropheryma whipplei is known mainly as the bacterial described (8). A case was defined as 2 positive quantita- T pathogen responsible for Whipple disease (1).
    [Show full text]
  • Bacteriology
    SECTION 1 High Yield Microbiology 1 Bacteriology MORGAN A. PENCE Definitions Obligate/strict anaerobe: an organism that grows only in the absence of oxygen (e.g., Bacteroides fragilis). Spirochete Aerobe: an organism that lives and grows in the presence : spiral-shaped bacterium; neither gram-positive of oxygen. nor gram-negative. Aerotolerant anaerobe: an organism that shows signifi- cantly better growth in the absence of oxygen but may Gram Stain show limited growth in the presence of oxygen (e.g., • Principal stain used in bacteriology. Clostridium tertium, many Actinomyces spp.). • Distinguishes gram-positive bacteria from gram-negative Anaerobe : an organism that can live in the absence of oxy- bacteria. gen. Bacillus/bacilli: rod-shaped bacteria (e.g., gram-negative Method bacilli); not to be confused with the genus Bacillus. • A portion of a specimen or bacterial growth is applied to Coccus/cocci: spherical/round bacteria. a slide and dried. Coryneform: “club-shaped” or resembling Chinese letters; • Specimen is fixed to slide by methanol (preferred) or heat description of a Gram stain morphology consistent with (can distort morphology). Corynebacterium and related genera. • Crystal violet is added to the slide. Diphtheroid: clinical microbiology-speak for coryneform • Iodine is added and forms a complex with crystal violet gram-positive rods (Corynebacterium and related genera). that binds to the thick peptidoglycan layer of gram-posi- Gram-negative: bacteria that do not retain the purple color tive cell walls. of the crystal violet in the Gram stain due to the presence • Acetone-alcohol solution is added, which washes away of a thin peptidoglycan cell wall; gram-negative bacteria the crystal violet–iodine complexes in gram-negative appear pink due to the safranin counter stain.
    [Show full text]
  • Cultivation and Viability Determination of Mycobacterium Leprae
    The International Textbook of Leprosy Part II Section 5 Chapter 5.3 Cultivation and Viability Determination of Mycobacterium leprae Ramanuj Lahiri National Hansen’s Disease Programs Linda B. Adams National Hansen’s Disease Programs Introduction Mycobacterium leprae, despite being recognized as a human pathogen over 140 years ago, re- mains uncultivable in microbiological culture media or in cell culture systems. Although it is now well established that M. leprae prefers cooler temperatures, slightly acidic microaerophilic condi- tions, and lipids rather than sugars as an energy source, the exact parameters for a defined axenic medium that would support the growth of M. leprae remain elusive. This failure to culture M. leprae ex vivo, along with its extremely slow growth rate in vivo, have been major obstacles in the understanding of vital molecular and cellular events in the pathogen- esis of leprosy. Moreover, investigations into bacterial metabolism and genetic manipulation of the organism are especially difficult when cloned mutants cannot easily undergo selection and isolation in pure culture. In this chapter, we briefly review attempts to cultivate this organism, alternate methods used to ascertain M. leprae viability, and the advantages and disadvantages of each application. The International Textbook of Leprosy Cultivation and Viability Cultivation of M. leprae EX VIVO ATTEMPTS In many microbiological studies, one of the major experimental endpoints is the determination of bacterial viability, which is fairly easy to achieve if the organism is cultivable on laboratory media. In introductory microbiology classes, one learns to isolate an organism in pure culture by streak- ing a plate and picking a colony.
    [Show full text]
  • Clinical Manifestations and Diagnosis of Whipple's Disease: Case Report
    CASE REPORT Clinical manifestations and diagnosis of Whipple’s disease: case report Manifestações clínicas e diagnóstico da doença de Whipple: relato de caso Henrique Carvalho Rocha1, Wóquiton Rodrigues Marques Martins2, Marcos Roberto de Carvalho3, Lígia Menezes do Amaral4 DOI: 10.5935/2238-3182.20150051 ABSTRACT Introduction: Whipple’s disease is a rare multisystemic infection whose causative agent 1 MD-Resident at the Internal Medicine Program at the University Hospital of the Federal University of Juiz de is the Gram-positive bacillus Tropheryma whippelii. It is characterized by a prolonged Fora – UFJF. Juiz de Fora, MG – Brazil. phase of nonspecific symptoms that delays diagnosis. The disease evolves with good re- 2 MD-Resident at the Neurology Program in the University Hospital of UFJF. Juiz de Fora, MG – Brazil. sponse to antibiotic therapy, good clinical and laboratory evolution, however, if not prop- 3 MD. Neurologist. Coordinator of the Internal Medicine erly treated it can be serious and fatal. This report describes a case of Whipple’s disease Residency Program at the University Hospital of UFJF. Juiz de Fora, MG – Brazil. with systemic manifestations. Case report: male patient, 60 years of age, 15 kg weight 4 MD. Master’s degree in Collective Health. Preceptor loss in one year, diarrhea, anorexia, poly arthralgia, and cutaneous-mucosa pallor. His in the Residency in Internal Medicine in the University weight was 45 kg with 18.7 body mass index. The complete propaedeutics revealed: 8.12 Hospital of UFJF. Juiz de Fora, MG – Brazil g/dL hemoglobin, negative viral serology and celiac disease markers; CT scan of abdo- men: lymphadenopathy in mesenteric and para-aortic chains; upper gastrointestinal endoscopy revealed areas of enanthematous pangastritis and biopsy with histopatho- logic findings compatible with Whipple’s disease, colonoscopy without alterations.
    [Show full text]
  • CNS Whipple's Disease Heralded by Retinal Vasculitis
    Open Access Journal of Ophthalmology CNS Whipple’s Disease Heralded by Retinal Vasculitis Thanh Le1*, Ramirez A2, O’Connor P2, Youssef O1, Agange N2, Dipti 1 1 Singh OD and Wentworth G Case Report 1Chief ophthalmologist at South Texas Veterans Health Care System, USA Volume 2 Issue 1 2Department of Ophthalmology, University of Texas Health Science Center, USA Received Date: June 06, 2017 Published Date: June 19, 2017 *Corresponding author: Thanh Le, VA Eye Clinic 8410 Datapoint Drive San Antonio, TX 78256, USA, Tel: 361-876-2071; E-mail: [email protected] Abstract Background: Whipple’s disease is a rare, chronic, multi-organ, bacterial infection. The most common presenting manifestation of Whipple’s disease is gastrointestinal symptoms such as abdominal pain, weight loss, diarrhea, and migratory non-deforming sero negative polyarthralgias. Although neuro-ophthalmologic symptoms are common in CNS Whipple’s disease, uveitis as a presenting sign is rare. Case Report: A 36-year-old black male presented with the initial complaint of left eye vision loss but left against medical advice, only to return nine weeks later with additional symptoms of right eye visual field loss. Ocular examination revealed panuveitis, vasculitis, optic nerve atrophy left eye, and right homonymous hemianopsia of both eyes. Extensive laboratory testings were all negative. A MRI imaging showed large enhancing lesions in the thalamus, temporal and parietal lobes. A brain biopsy revealed periodic acid-Schiff reagent (PAS)-positive intracytoplasmic organisms within multiple macrophages, consistent with Whipple’s disease. After two months of antibiotic therapy, the patient’s symptoms and MRI findings were markedly improved.
    [Show full text]
  • Tropheryma Whipplei Twist: a Human Pathogenic Actinobacteria with A
    Article Tropheryma whipplei Twist: A Human Pathogenic Actinobacteria With a Reduced Genome Didier Raoult,1,3 Hiroyuki Ogata,2 Ste´phane Audic,2 Catherine Robert,1 Karsten Suhre,2 Michel Drancourt,1 and Jean-Michel Claverie2,3 1Unite´ des Rickettsies, Faculte´deMe´decine, CNRS UMR6020, Universite´delaMe´diterrane´e, 13385 Marseille Cedex 05, France; 2Information Ge´nomique et Structurale, CNRS UPR2589,13402 Marseille Cedex 20, France The human pathogen Tropheryma whipplei is the only known reduced genome species (<1 Mb) within the Actinobacteria [high G+C Gram-positive bacteria]. We present the sequence of the 927,303-bp circular genome of T. whipplei Twist strain, encoding 808 predicted protein-coding genes. Specific genome features include deficiencies in amino acid metabolisms, the lack of clear thioredoxin and thioredoxin reductase homologs, and a mutation in DNA gyrase predicting a resistance to quinolone antibiotics. Moreover, the alignment of the two available T. whipplei genome sequences (Twist vs. TW08/27) revealed a large chromosomal inversion the extremities of which are located within two paralogous genes. These genes belong to a large cell-surface protein family defined by the presence of a common repeat highly conserved at the nucleotide level. The repeats appear to trigger frequent genome rearrangements in T. whipplei, potentially resulting in the expression of different subsets of cell surface proteins. This might represent a new mechanism for evading host defenses. The T. whipplei genome sequence was also compared to other reduced bacterial genomes to examine the generality of previously detected features. The analysis of the genome sequence of this previously largely unknown human pathogen is now guiding the development of molecular diagnostic tools and more convenient culture conditions.
    [Show full text]
  • Whipple's Disease: a Review
    ANNALS OF GASTROENTEROLOGY 2004, 17(1):43-50 Review Whipples disease: a review M. Pyrgioti, A. Kyriakidis SUMMARY eryma which means barrier and the name of the man who recognized the first case of the disease George Hoyt Whipples disease was described in 1907 and given the name Whipple.1 The most common symptoms are diarrhea and intestinal lipodystrophy until it was found that the agent weight loss, but there are a lot of other manifestations that responsible is a bacterium named Tropheryma whipplei. may not concern the small bowel, like the involvement of Its a rare disease which occurs predominantly in males mesenteric lymph nodes, athralgias, fever, central nervous aged 30-60. The small intestinal mucosa is always affected system disorders and involvement of the eye. with lesions that are specific to this disease. Replacement of most of cellular elements in the lamina propria by macrophages is characteristic of Whipples disease. It is a HISTORICAL BACKGROUND systemic disease that can affect every system, usually Allchin and Hebb reported the first case of Whipples causing symptoms in the bowel, the joints, the central disease in 1895 without realizing then that it was a special nervous and the cardiovascular systems. The diagnosis of disease. George Hoyt Whipple, in 1907, recognized the Whipples disease is not easy and depends on a combination first case of the disease that now bears his name. His of clinical features, the characteristic histopathological patient was a 36 year-old doctor, who had gradual weigh findings, the presence of pathognomonic PAS positive loss, indefinite abdominal signs and polyarthritis.2 His macrophages and the PCR of the 16S ribosomal RNA of stools consisted of neutral fat and fatty acids.
    [Show full text]
  • Prosthetic Joint Infection Diagnosis Using Conventional Methods
    11/5/2018 Prosthetic Joint Infection Diagnosis Using Conventional Methods HOT TOPIC / 2018 ©MFMER Presenter: Robin Patel, M.D. Professor of Medicine and Microbiology Chair, Division of Clinical Microbiology and the Elizabeth P. and Robert E. Allen Professor of Individualized Medicine Department of Laboratory Medicine and Pathology at Mayo Clinic, Rochester, Minnesota ©MFMER 1 11/5/2018 Disclosures • Dr. Robin Patel has a US patent for a method and an apparatus for sonication, but has foregone her right to personally receive royalties. Funding • National Institutes of Health • Department of Defense • National Science Foundation ©MFMER Total Hip and Knee Replacement Procedures United States1 Total knee Total hip Year ©MFMER 2 11/5/2018 ©MFMER Prosthetic Hip and Knee Infections: United States2 2001‐2020 ©MFMER 3 11/5/2018 Surgical Management of Prosthetic Hip or Knee Infection3 Reprinted with permission from Massachusetts Medical Society. ©MFMER Prosthetic Joint Infection Microbiology4 Hip and Knee Hip Knee Shoulder Elbow All time periods Early Number of joints 2435 637 1979 1427 199 110 Staphylococcus aureus 27 38 13 23 18 42 Coagulase negative staphylococci 27 22 30 23 41 41 Streptococcus species 846644 Enterococcus species 310223 0 Aerobic gram negative bacilli 92475107 Anaerobic bacteria 4395 Cutibacterium acnes 24 1 Other anaerobes 30 Culture negative 14 10 7 11 15 5 Polymicrobial 15 31 14 12 16 3 Other 3 ©MFMER 4 11/5/2018 Unusual Causes of Prosthetic Joint Infection5 Actinomyces israelii Granulicatella adiacens Aspergillus fumigatus
    [Show full text]
  • Whipple´S Disease, a Rare Malabsorption Syndrome of Late Diagnosis
    CASO CLÍNICO Whipple´s disease, a rare malabsorption syndrome of late diagnosis. Raquel Batista, André Real , Jorge Nepomuceno, Maria de Fátima Pimenta AL ÍNDICE VOLVER PULSE PARA Serviço de Medicina Interna, Centro Hospitalar Médio Tejo, Abrantes, Portugal Abstract Whipple´s disease is a rare, chronic bacterial illness with multisystemic involvement, caused by Tropheryma whipplei. Due to it´s multiform presentation Galicia Clínica | Sociedade Galega de Medicina Interna and rarity it is often misdiagnosed. The standard method concerning diagnosis is the detection of PAS (periodic acid- Shiff) positive macrophages in affected tissues.Immunohistochemical staining and PCR (polymerase chain reaction) increase the sensitivity and specificity of conventional methods. Long term antibiotic therapy provides a favourable outcome in the majority of cases. The autors describe a case of a patient with Whipple´s disease in a progressive stage. Keywords: Whipple´s disease. Malabsorption syndrome. Tropheryma whipplei Palabras clave: Enfermedad de Whipple. Síndrome de malabsorción. Tropheryma whipplei Introduction Case report The Whipple´s disease is a rare multisystemic infection cau- A fifty four year old female caucasian patient was admitted to the sed by Tropheryma whipplei , a gram positive bacterium whi- emergency room for investigation of a 17 kg weight loss with asthe- ch is taxonomically closely related to the group of Actinomy- nia, anemia and intermittent diarrhea without blood, mucus or pus for ces and Mycobacteria1.It is an important cause of infectious about one year. Her previous medical history included 2 years of lom- malabsorption syndrome that affects about 1 in 1 000 000 bar pain with mechanical characteristics. At the admission, the patient people, being affected mainly men 40 to 50 years2.
    [Show full text]
  • Pulmonary-Coinfection-Of-Mycobacterium-Tuberculosis-And-Tropheryma-Whipplei-A-Case
    Zhu et al. J Med Case Reports (2021) 15:359 https://doi.org/10.1186/s13256-021-02899-y CASE REPORT Open Access Pulmonary coinfection of Mycobacterium tuberculosis and Tropheryma whipplei: a case report Binghua Zhu1, Jing Tang2, Rong Fang1, Xuejie Fei1, Qing Wang1, Wenqing Wang1, Xueqin Wu3, Chao Liu3* and Qian Wang1* Abstract Background: We diagnosed a clinical case of pulmonary infection involving Mycobacterium tuberculosis and Tro- pheryma whipplei in a patient with acute respiratory distress syndrome. The diagnosis was assisted by metagenomic next-generation sequencing of bronchoalveolar lavage fuid. Case presentation: A 44-year-old Han Chinese inmate was transferred to the emergency department because of dry cough, chest tightness, and shortness of breath. The patient’s body temperature rose to 39.3 °C following empiri- cal cephalosporin treatment for 1 week. The blood CD4 /CD8 ratio was 0.7, suggesting immunodefciency. Routine microbiological tests were performed, and tuberculosis +interferon+ gamma release assays were positive. Mycobacte- rium tuberculosis polymerase chain reaction was also positive. Chest computed tomography scan revealed miliary nodules and ground-glass opacifcations, which were in accordance with tuberculosis. To fully examine the etiology, we performed routine laboratory tests and metagenomic sequencing, the results of which indicated the presence of Mycobacterium tuberculosis and Tropheryma whipplei. We administered anti-tuberculosis regimen in combination with trimethoprim/sulfamethoxazole. The patient recovered, with chest computed tomography scan showing absorption of lesions. Conclusions: Compared with traditional diagnostic methods such as culture and serology, metagenomic next-gen- eration sequencing has the advantage of detecting a wide array of microorganisms in a single test and therefore can be used for clinical diagnosis of rare pathogens and microbial coinfections.
    [Show full text]