Bartonella Clarridgeiae Bacteremia Detected In An Asymptomatic Blood Donor

Human exposure to Bartonella clarridgeiae has been reported only on the basis of antibody detection. We report for the first time an asymptomatic human blood donor infected with B. clarridgeiae, as documented by enrichment blood culture, PCR, and DNA sequencing.531352356Maggi, R.G., Duncan, A.W., Breitschwerdt, E.B., Novel chemically modified liquid medium that will support the growth of seven Bartonella species (2005) J Clin Microbiol, 43, pp. 2651-2655. , http://dx.doi.org/10.1128/JCM.43.6.2651-2655.2005Drummond, M.R., Pitassi, L.H., Lania, B.G., Dos Santos, S.R., Gilioli, R., Velho, P.E., Detection of Bartonella henselae in defibrinated sheep blood used for culture media supplementation (2011) Braz J Microbiol, 42, pp. 430-432. , http://dx.doi.org/10.1590/S1517-83822011000200003Altschul, S.F., Gish, W., Miller, W., Myers, E.W., Lipman, D.J., Basic local alignment search tool (1990) J Mol Biol, 215, pp. 403-410Dalton, M.J., Robinson, L.E., Cooper, J., Regnery, R.L., Olson, J.G., Childs, J.E., Use of Bartonella antigens for serologic diagnosis of cat-scratch disease at a national referral center (1995) Arch Intern Med, 155, pp. 1670-1676Breitschwerdt, E.B., Maggi, R.G., Chomel, B.B., Lappin, M.R., Bartonellosis: An emerging infectious disease of zoonotic importance to animals and human beings (2010) J Vet Emerg Crit Care (San Antonio), 20, pp. 8-30. , http://dx.doi.org/10.1111/j.1476-4431.2009.00496.xChamberlin, J., Laughlin, L.W., Romero, S., Solorzano, N., Gordon, S., Andre, R.G., Pachas, P., Watts, D., Epidemiology of endemic Bartonella bacilliformis: A prospective cohort study in a Peruvian mountain valley community (2002) J Infect Dis, 186, pp. 983-990. , http://dx.doi.org/10.1086/344054Maggi, R.G., Ericson, M., Mascarelli, P.E., Bradley, J.M., Breitschwerdt, E.B., Bartonella henselae bacteremia in a mother and son potentially associated with tick exposure (2013) Parasit Vectors, 6, p. 101. , http://dx.doi.org/10.1186/1756-3305-6-101Scott, M.A., McCurley, T.L., Vnencak-Jones, C.L., Hager, C., McCoy, J.A., Anderson, B., Collins, R.D., Edwards, K.M., Cat scratch disease: Detection of Bartonella henselae DNA in archival biopsies from patients with clinically, serologically, and histologically defined disease (1996) Am J Pathol, 149, pp. 2161-2167Slater, L.N., Welch, D.F., Min, K.W., Rochalimaea henselae causes bacillary angiomatosis and peliosis hepatis (1992) Arch Intern Med, 152, pp. 602-606Sander, A., Zagrosek, A., Bredt, W., Schiltz, E., Piemont, Y., Lanz, C., Dehio, C., Characterization of Bartonella clarridgeiae flagellin (FlaA) and detection of antiflagellin antibodies in patients with lymphadenopathy (2000) J Clin Microbiol, 38, pp. 2943-2948Kordick, D.L., Hilyard, E.J., Hadfield, T.L., Wilson, K.H., Steigerwalt, A.G., Brenner, D.J., Breitschwerdt, E.B., Bartonella clarridgeiae, a newly recognized zoonotic pathogen causing inoculation papules, fever, and lymphadenopathy (cat scratch disease) (1997) J Clin Microbiol, 35, pp. 1813-1818Margileth, A.M., Baehren, D.F., Chest-wall abscess due to cat-scratch disease (CSD) in an adult with antibodies to Bartonella clarridgeiae: Case report and review of the thoracopulmonary manifestations of CSD (1998) Clin Infect Dis, 27, pp. 353-357. , http://dx.doi.org/10.1086/514671Chomel, B.B., Mac Donald, K.A., Kasten, R.W., Chang, C.C., Wey, A.C., Foley, J.E., Thomas, W.P., Kittleson, M.D., Aortic valve endocarditis in a dog due to Bartonella clarridgeiae (2001) J Clin Microbiol, 39, pp. 3548-3554. , http://dx.doi.org/10.1128/JCM.39.10.3548-3554.2001Gillespie, T.N., Washabau, R.J., Goldschmidt, M.H., Cullen, J.M., Rogala, A.R., Breitschwerdt, E.B., Detection of Bartonella henselae and Bartonella clarridgeiae DNA in hepatic specimens from two dogs with hepatic disease (2003) J Am Vet Med Assoc, 222, pp. 47-51. , http://dx.doi.org/10.2460/javma.2003.222.47, 35Robinson, M.T., Hillman, T., Langton, D.A., Shaw, S.E., Bartonella clarridgeiae in a cat in the UK (2009) Vet Rec, 164, pp. 58-59. , http://dx.doi.org/10.1136/vr.164.2.58Sykes, J.E., Westropp, J.L., Kasten, R.W., Chomel, B.B., Association between Bartonella species infection and disease in pet cats as determined using serology and culture (2010) J Feline Med Surg, 12, pp. 631-636. , http://dx.doi.org/10.1016/j.jfms.2010.04.003Fouch, B., Coventry, S., A case of fatal disseminated Bartonella henselae infection (cat-scratch disease) with encephalitis (2007) Arch Pathol Lab Med, 131, pp. 1591-1594Boudebouch, N., Sarih, M., Beaucournu, J.C., Amarouch, H., Hassar, M., Raoult, D., Parola, P., Bartonella clarridgeiae, B. Henselae, and Rickettsia felis in fleas from Morocco (2011) Ann Trop Med Parasitol, 105, pp. 493-498. , http://dx.doi.org/10.1179/1364859411Y.0000000038Kordick, D.L., Brown, T.T., Shin, K., Breitschwerdt, E.B., Clinical and pathologic evaluation of chronic Bartonella henselae or Bartonella clarridgeiae infection in cats (1999) J Clin Microbiol, 37, pp. 1536-1547Chomel, B.B., Carlos, E.T., Kasten, R.W., Yamamoto, K., Chang, C.C., Carlos, R.S., Abenes, M.V., Pajares, C.M., Bartonella henselae and Bartonella clarridgeiae infection in domestic cats from the Philippines (1999) Am J Trop Med Hyg, 60, pp. 593-597Dehio, C., Bartonella interactions with endothelial cells and erythrocytes (2001) Trends Microbiol, 9, pp. 279-285. , http://dx.doi.org/10.1016/S0966-842X(01)02047-9Dehio, C., Meyer, M., Berger, J., Schwarz, H., Lanz, C., Interaction of Bartonella henselae with endothelial cells results in bacterial aggregation on the cell surface and the subsequent engulfment and internalisation of the bacterial aggregate by a unique structure, the invasome (1997) J Cell Sci, 110 (18), pp. 2141-2154Braga Mdo, S., Diniz, P.P., André, M.R., Bortoli, C.P., Machado, R.Z., Molecular characterisation of Bartonella species in cats from São Luís, state of Maranhão, North-Eastern Brazil (2012) Mem Inst Oswaldo Cruz, 107, pp. 772-777. , http://dx.doi.org/10.1590/S0074-02762012000600011Eremeeva, M.E., Gerns, H.L., Lydy, S.L., Goo, J.S., Ryan, E.T., Mathew, S.S., Ferraro, M.J., Koehler, J.E., Bacteremia, fever, and splenomegaly caused by a newly recognized Bartonella species (2007) N Engl J Med, 356, pp. 2381-2387. , http://dx.doi.org/10.1056/NEJMoa065987Chomel, B.B., Boulouis, H.J., Breitschwerdt, E.B., Kasten, R.W., Vayssier-Taussat, M., Birtles, R.J., Koehler, J.E., Dehio, C., Ecological fitness and strategies of adaptation of Bartonella species to their hosts and vectors (2009) Vet Res, 40, p. 29. , http://dx.doi.org/10.1051/vetres/2009011Breitschwerdt, E.B., Maggi, R.G., Duncan, A.W., Nicholson, W.L., Hegarty, B.C., Woods, C.W., Bartonella species in blood of immunocompetent persons with animal and arthropod contact (2007) Emerg Infect Dis, 13, pp. 938-941. , http://dx.doi.org/10.3201/eid1306.061337Carson, J.L., Grossman, B.J., Kleinman, S., Tinmouth, A.T., Marques, M.B., Fung, M.K., Holcomb, J.B., Djulbegovic, B., Red blood cell transfusion: A clinical practice guideline from the AABB (2012) Ann Intern Med, 157, pp. 49-58. , http://dx.doi.org/10.7326/0003-4819-157-1-201206190-00429Ramirez-Arcos, S., Goldman, M., Blajchman, M., Bacterial contamination (2012) Transfusion Reaction, 4, pp. 153-189. , Popovsky MA (ed), American Association Of Blood Banks, Bethesda, MDVamvakas, E.C., Blajchman, M.A., Transfusion-related mortality: The ongoing risks of allogeneic blood transfusion and the available strategies for their prevention (2009) Blood, 113, pp. 3406-3417. , http://dx.doi.org/10.1182/blood-2008-10-167643Magalhães, R.F., Cintra, M.L., Barjas-Castro, M.L., Del Negro, G.M., Okay, T.S., Velho, P.E., Blood donor infected with Bartonella henselae (2010) Transfus Med, 20, pp. 280-282. , http://dx.doi.org/10.1111/j.1365-3148.2010.01001.xMagalhães, R.F., Pitassi, L.H., Salvadego, M., De Moraes, A.M., Barjas-Castro, M.L., Velho, P.E., Bartonella henselae survives after the storage period of red blood cell units: Is it transmissible by transfusion? (2008) Transfus Med, 18, pp. 287-291. , http://dx.doi.org/10.1111/j.1365-3148.2008.00871.xLin, J.W., Chen, C.M., Chang, C.C., Unknown fever and back pain caused by Bartonella henselae in a veterinarian after a needle puncture: A case report and literature review (2011) Vector Borne Zoonotic Dis, 11, pp. 589-591. , http://dx.doi.org/10.1089/vbz.2009.0217Oliveira, A.M., Maggi, R.G., Woods, C.W., Breitschwerdt, E.B., Suspected needle stick transmission of Bartonella vinsonii subspecies berkhoffii to a veterinarian (2010) J Vet Intern Med, 24, pp. 1229-1232. , http://dx.doi.org/10.1111/j.1939-1676.2010.0563.xOhl, M.E., Spach, D.H., Bartonella quintana and urban trench fever (2000) Clin Infect Dis, 31, pp. 131-135. , http://dx.doi.org/10.1086/313890Daly, J.S., Worthington, M.G., Brenner, D.J., Moss, C.W., Hollis, D.G., Weyant, R.S., Steigerwalt, A.G., O'Connor, S.P., Rochalimaea elizabethae sp. Nov. Isolated from a patient with endocarditis (1993) J Clin Microbiol, 31, pp. 872-881Oksi, J., Rantala, S., Kilpinen, S., Silvennoinen, R., Vornanen, M., Veikkolainen, V., Eerola, E., Pulliainen, A.T., Cat scratch disease caused by Bartonella grahamii in an immunocompromised patient (2013) J Clin Microbiol, 51, pp. 2781-2784. , http://dx.doi.org/10.1128/JCM.00910-13Breitschwerdt, E.B., Mascarelli, P.E., Schweickert, L.A., Maggi, R.G., Hegarty, B.C., Bradley, J.M., Woods, C.W., Hallucinations, sensory neuropathy, and peripheral visual deficits in a young woman infected with Bartonella koehlerae (2011) J Clin Microbiol, 49, pp. 3415-3417. , http://dx.doi.org/10.1128/JCM.00833-11Raoult, D., Roblot, F., Rolain, J.M., Besnier, J.M., Loulergue, J., Bastides, F., Choutet, P., First isolation of Bartonella alsatica from a valve of a patient with endocarditis (2006) J Clin Microbiol, 44, pp. 278-279. , http://dx.doi.org/10.1128/JCM.44.1.278-279.2006Welch, D.F., Carroll, K.C., Hofmeister, E.K., Persing, D.H., Robison, D.A., Steigerwalt, A.G., Brenner, D.J., Isolation of a new subspecies, Bartonella vinsonii subsp. Arupensis, from a cattle rancher: Identity with isolates found in conjunction with Borrelia burgdorferi and Babesia microti among naturally infected mice (1999) J Clin Microbiol, 37, pp. 2598-2601Probert, W., Louie, J.K., Tucker, J.R., Longoria, R., Hogue, R., Moler, S., Graves, M., Fritz, C.L., Meningitis due to a "Bartonella washoensis"-like human pathogen (2009) J Clin Microbiol, 47, pp. 2332-2335. , http://dx.doi.org/10.1128/JCM.00511-09Kosoy, M., Morway, C., Sheff, K.W., Bai, Y., Colborn, J., Chalcraft, L., Dowell, S.F., Petersen, L.R., Bartonella tamiae sp. Nov., a newly recognized pathogen isolated from three human patients from Thailand (2008) J Clin Microbiol, 46, pp. 772-775. , http://dx.doi.org/10.1128/JCM.02120-07Maggi, R.G., Kosoy, M., Mintzer, M., Breitschwerdt, E.B., Isolation of Candidatus Bartonella melophagi from human blood (2009) Emerg Infect Dis, 15, pp. 66-68. , http://dx.doi.org/10.3201/eid1501.081080Lin, E.Y., Tsigrelis, C., Baddour, L.M., Lepidi, H., Rolain, J.M., Patel, R., Raoult, D., Candidatus Bartonella mayotimonensis and endocarditis (2010) Emerg Infect Dis, 16, pp. 500-503. , http://dx.doi.org/10.3201/eid1603.081673Breitschwerdt, E.B., Maggi, R.G., Cadenas, M.B., De Paiva Diniz, P.P., A groundhog, a novel Bartonella sequence, and my father's death (2009) Emerg Infect Dis, 15, pp. 2080-2086. , http://dx.doi.org/10.3201/eid1512.AD151

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma

The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant patterns between AI and pathologists had notably higher intratumoral heterogeneity. Furthermore, ANORAK facilitates the morphological and spatial assessment of the acinar pattern, capturing acinus variations with pattern transition. Collectively, our AI method enabled the precision quantification and morphology investigation of growth patterns, reflecting intratumoral histological transitions in lung adenocarcinoma