Acute multifocal retinitis in a patient with Q fever (Coxiella Burnetii infection) with endocarditis

Acute multifocal retinitis in a patient with Q fever (Coxiella Burnetii infection) with endocarditis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Acute multifocal retinitis in a patient with Q fever (Coxiella Burnetii infection) with endocarditis Anis Mahmoud, Fatma Abid, Molka Khairallah, Sofien Affes, Sameh Mbarek, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1454220/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Objective To report acute multifocal retinitis in association with serologically-proven Coxiella (C) Burnetii infection (Q fever) with endocarditis. Material and methods A single case report documented with multimodal imaging. Results A 67-year-old cattle breeder presented with a 2-week history of persistent fever, headache, and floaters in both eyes. On examination, his best-corrected visual acuity was 20/20, and there was 1+ vitreous cells in both eyes. Bilateral fundus examination showed multiple small superficial white retinal lesions scattered in the posterior pole and midperiphery associated with a few retinal hemorrhages. These retinal lesions did not stain on fluorescein angiography (FA) and showed focal hyperreflectivity and thickening primarily involving the inner retinal layers on optical coherence tomography (OCT). There also was a band-like hyper-reflective area in the middle retina consistent with paramacular acute middle maculopathy. Transthoracic echocardiogram (TTE) showed a mobile echodensity on the anterior aortic leaflet consistent with a diagnosis of endocarditis. Elisa assays performed on paired serum samples collected 2 weeks apart showed increase in antibodies against C burnetii from 60 IU/ml to 255 IU/ml. The patient was treated with doxycycline 100 mg twice a day for 18 months, with subsequent resolution of the endocarditis. Sequential ocular examinations showed gradual resolution of all acute retinal findings without visible scars. Conclusion: Acute Q fever, caused by C burnetii infection, should be considered in the differential diagnosis of acute multifocal retinitis. A systematic cardiac assessment with echocardiography is essential for early diagnosis of associated endocarditis and for prompt administration of appropriate antibiotic treatment to improve clinical outcomes . Acute multifocal retinitis Acute Q fever Coxiella burnetii endocarditis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Q fever is a worldwide distributed zoonosis caused by C burnetii , an obligate gram-negative intracellular organism [ 1 ]. It is primarily transmitted to humans through inhalation of aerosols from contaminated soil or animal waste, with cattle, sheep, and goats being the main reservoirs. Incubation period ranges from 2 to 50 days with a median of 18 days [ 2 ]. Most patients remain asymptomatic or develop a nonspecific and self-limiting febrile illness, so that Q fever remains frequently undiagnosed. Endocarditis is the most common and most serious manifestation of chronic Q fever, but other severe acute or chronic complications also have been described including pneumonia, hepatitis, osteomyelitis, endovascular infection, and involvement of the central nervous system [ 3 , 4 ]. Ocular involvement has rarely been described in the course of Q fever including anterior and posterior uveitis, optic neuropathy, exudative retinal detachment, and abducens palsy [ 5 ]. We herein describe a patient who developed acute multifocal retinitis (AMR) in association with acute C burnetii infection with endocarditis. Case Report A 67-year-old cattle breeder presented to the emergency department with a 2-week history of persistent fever, headache, and floaters in both eyes. On examination, his best-corrected visual acuity was 20/20 in both eyes. There was no relative afferent pupillary defect, and the ocular motility examination was normal for both eyes. Slit-lamp examination showed a quiet anterior chamber and 1 + vitreous cells bilaterally. Intraocular pressure was 12 mmHg in both eyes. Fundus examination revealed multiple white spots at the level of the inner retina, measuring 200 to 500 microns, scattered in the posterior pole and midperiphery in both eyes. There also were a few retinal hemorrhages, with some them having a white center. A flat, well-circumscribed chorioretinal lesion associating atrophic and hyperpigmented areas was seen along the superotemporal vascular arcade in the left eye (LE) ( Fig. 1 ) . FA showed a masking effect from retinal hemorrhages, a slight hypofluorescence of retinal infiltrates without late staining, and peripheral retinal vascular leakage ( Fig. 2 ) . Swept source-OCT scan (Topcon, DRI triton) through a retinal infiltrate in the LE revealed a focal area of retinal hyperreflective thickening extending from the retinal nerve fiber layer to the outer retinal layers, with sparing of the retinal pigment epithelium and choroid. There also was a band-like hyper-reflective area in the middle retina consistent with paramacular acute middle maculopathy (PAMM) ( Fig. 3 ) . Cardiac examination showed a diastolic decrescendo murmur. TTE showed a mobile echodensity on the anterior aortic leaflet measuring 20 x 14 mm consistent with a diagnosis of endocarditis ( Fig. 4 ) . Repeated blood cultures were negative. A lumbar puncture was performed revealing an aseptic meningitis with increased lymphocyte and protein levels. Laboratory testing was negative for bartonellosis, rickettsial infection, syphilis, and tuberculosis. The diagnosis of acute Q fever was made on the basis of SERION ELISA results with positive C burnetii phase II IgM and increase in IgG titers from 60 IU/ml to 255 IU/ml on paired serum samples collected 2 weeks apart. The patient was treated with doxycycline 100 mg twice a day for 18 months. Six weeks after initial presentation, the patient reported the disappearance of floaters. Fundus examination showed a complete resolution of retinal hemorrhages and multifocal retinal lesions, with no residual chorioretinal scars ( Fig. 5 ) . Sequential TTE over a two-month follow-up period showed gradual regression of the endocardial vegetation. Discussion To the best our knowledge, our report is the first to describe the association of AMR with a serologically proven systemic C burnetii infection. AMR, previously termed acute multifocal inner retinitis, has been considered to be often idiopathic, but several infectious etiologies have been recognized including cat scratch disease, rickettsial infection, and syphilis [ 6 – 9 ]. Recent data from Tunisia show rickettsial disease, including rickettsia conorii and rickettsia typhi, to be the most common cause of AMR [ 10 ]. In the present case, serological testing showed negative results for rickettsial infection and also for cat scratch disease and syphilis. The presence of an associated blood-culture negative endocarditis in a patient with a history of animal contact raised our suspicion of Q fever. The diagnosis was confirmed by the detection of high titers of anti- C burnetii antibodies and the patient accordingly was treated with oral doxycycline. The ocular disease pattern of our patient conformed to most of the previously reported features of AMR, especially with regard to the systemic febrile illness, minimal vision impairment, characteristic multiple inner retinitis spots associated with mild vitritis, and benign and self-limiting clinical course. Endocarditis has been considered as an almost exclusive complication of chronic Q fever. Our findings, consistent with previous recent data, show that acute endocarditis, readily detectable with TTE, can affect a sizable subset of patients with acute Q fever [ 11 – 13 ]. Therefore, early diagnosis of Q fever and associated endocardial involvement is of utmost importance for prompt initiation of antibiotic treatment to prevent persistent endocarditis and related morbidity and mortality. Multifocal superficial retinal infiltrates associated with Q fever may result from intraretinal multiplication of C burnetii , or from immune-mediated response to bacterial antigens caused by the deposition of immune complexes, inflammatory cells, or antibodies through retinal vessels [ 14 – 16 ]. The vascular tropism of C burnetii also is reflected in our patient in the presence of associated retinal hemorrhages, retinal vascular leakage, and retinal vascular occlusion in the form of PAMM. This case shows that C burnetii infection should be considered in the differential diagnosis of AMR associated with systemic febrile illness. Serological confirmation is required for a definitive diagnosis that could be challenging. A systematic echocardiography is of utmost importance for early detection of disease-related endocarditis and for prompt administration of appropriate antibiotic treatment to improve clinical outcomes. Abbreviations AMR Acute Multifocal Retinitis C Coxiella FA Fluorescein Angiography LE Left Eye OCT Optical Coherence Tomography PAMM Paramacular Acute Middle Maculopathy TTE Transthoracic Echocardiogram Declarations Ethics approval and consent to participate : Informed consent was obtained from our patient. Consent for publication : Oral and written consent to publication of the case was obtained from the patient. This report does not contain any personal information that could lead to the identification of the patient. Availability of data and material : The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests : None of the authors has any financial/conflicting interests to disclose Funding : Authors received no funding Authors' contributions : All authors contributed to the study concept and design, and all authors acquired and interpreted study data. AM, FA, MK, SA, HIHA and ABHK collected data. AM, FA, MK and SM drafted the manuscript. RM and MK provided critical manuscript revisions and supervised the study. All authors read and approved the final manuscript. Acknowledgements : Ministry of Higher Education and Research of Tunisia References Angelakis E, Raoult D. Q Fever. Vet Microbiol 2010;140:297-309. Todkill D, Fowler T, Hawker JI. Estimating the incubation period of acute Q fever, a systematic review. Epidemiol Infect. 2018;146(6): 665–72. Derrick EH. “Q” fever, new fever entity: clinical features, diagnosis and laboratory investigation. Med J Aust 1973;2:281–299. Kazar J (2005) Coxiella burnetii infection. Ann N Y Acad Sci 1063:105–114. Million M, Halfon J, Le Lez ML, Drancourt M, Raoult D. Relapsing uveitis and optic neuritis due to chronic Q fever. British journal of ophthalmology. 2011 Jul;95(7):1026-7, 1038-9. doi:10.1136/bjo.2009.169615. Jones MR, Cunningham ET Jr (1997) Bartonella henselae-associated AMR in a patient with acquired immunodeficiency syndrome. Retina 17(5):457–459 Lukas JR, Egger S, Parschalk B, Stur M (1998) Bilateral small retinal infiltrates during rickettsial infection. Br J Ophthalmol 82:1217–1218 Khairallah M, Ben Yahia S, Toumi A, Jelliti B, Loussaief C, Romdhane FB, Messaoud R, Chakroun M (2009) Ocular manifestations associated with murine typhus. Br J Ophthalmol 93(7):938–942 Cunningham ET Jr, Schatz H, McDonald HR, Johnson RN (1997) Acute multifocal retinitis. Am J Ophthalmol 123(3):347–357 Khochtali, S. Gargouri, S. Zina, I. Ksiaa, N. Abroug, S. Zaouali, et al., Acute multifocal retinitis: a retrospective review of 35 cases, J Ophthalmic Inflamm Infect 8 (1) (2018) 18. Million M, Thuny F, Bardin N, Angelakis E, Edouard S, Bessis S, et al. Antiphospholipid Antibody Syndrome with Valvular Vegetations in Acute Q Fever. Clin Infect Dis.2016; 62:537 –44. Bitsori M, Vergadi E, Germanakis I, Raissaki M, Galanakis E. Case Report: Α Case of Endocarditis and Embolic Stroke in a Child, Suggestive of Acute Q Fever Infection. Am J Trop Med Hyg. 2020;103(4):1435-1438. Melenotte C, Epelboin L, Million M, Hubert S, Monsec T, Djossou F et al. Acute Q Fever Endocarditis: A Paradigm Shift Following the Systematic Use of Transthoracic Echocardiography During Acute Q Fever. Clin Infect Dis.2019. 13;69(11):1987-1995. Cunningham ET Jr, Schatz H, McDonald HR, Johnson RN (1997) Acute multifocal retinitis. Am J Ophthalmol 123(3):347–357 Khairallah M, Ladjimi A, Chakroun M, Messaoud R, Yahia SB, Zaouali S, Romdhane FB, Bouzouaia N (2004) Posterior segment manifestations of Rickettsia conorii infection. Ophthalmology 111(3):529–534 Lumio J, Penttinen K, Pettersson T. Q fever in Finland: clinical, immunological and epidemiological findings. Scand J Infect Dis. 1981;13: 17–21 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 19 Apr, 2022 Reviews received at journal 15 Apr, 2022 Reviewers agreed at journal 22 Mar, 2022 Reviewers invited by journal 19 Mar, 2022 Submission checks completed at journal 15 Mar, 2022 Editor assigned by journal 15 Mar, 2022 First submitted to journal 15 Mar, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1454220","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":90979245,"identity":"69349560-18a5-441a-b309-1368f0822d82","order_by":0,"name":"Anis Mahmoud","email":"","orcid":"","institution":"Department of Ophthalmology, Tahar Sfar University Hospital, Mahdia, Faculty of Medicine, University of Monastir, Monastir, 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12:59:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1454220/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1454220/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":19336426,"identity":"51a52422-df9d-4393-bb10-ebcf5742150b","added_by":"auto","created_at":"2022-03-17 16:25:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":207313,"visible":true,"origin":"","legend":"\u003cp\u003eBaseline composite fundus photography shows bilateral small yellow-white retinal lesions in the posterior pole and the periphery (red arrows), with a few retinal hemorrhages, some of which are white-centered (yellow arrow).\u0026nbsp;Note the presence of an old, flat, well-delineated atrophic and pigmented lesion along the superotemporal retinal vascular arcade in the left eye.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1454220/v1/6c3d28eccb95128004a85972.png"},{"id":19336185,"identity":"ca9b0ec9-ae47-49ab-84b4-047ca37bbaa3","added_by":"auto","created_at":"2022-03-17 16:22:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":144035,"visible":true,"origin":"","legend":"\u003cp\u003eFluorescein angiography shows hypofluorescence by blockage from retinal hemorrhages, peripheral retinal vascular leakage in the right eye (arrow), and no staining of retinal infiltrates. The superotempoareal atrophic area in the left eye shows hypofluorescence with visibility of choroidal vessels.\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-1454220/v1/2f7befdf97a1dc8c94e07f1d.png"},{"id":19336186,"identity":"b5c3b5b8-9ca0-421d-ab2c-6405818b5cc7","added_by":"auto","created_at":"2022-03-17 16:22:14","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":216504,"visible":true,"origin":"","legend":"\u003cp\u003eSwept source OCT scan of the LE passing through a retinal infiltrate shows hyperreflective preretinal vitreous dots and a focal area of thickened, hyperreflective inner retina with infiltration extending from the nerve fiber layer to the outer retinal layers, with the ellipsoid zone, retinal pigment epithelium, and choroid clearly delineated and spared (red arrow). Note the presence of a band-like hyperreflective area in the middle retina suggestive of PAMM (yellow arrow).\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-1454220/v1/7b3f0207ee381654a3fbaeba.png"},{"id":19336189,"identity":"09a9734e-3e3f-415f-be53-20dc04580930","added_by":"auto","created_at":"2022-03-17 16:22:15","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":140701,"visible":true,"origin":"","legend":"\u003cp\u003eTransthoracic echocardiogram a mobile echodensity on the anterior aortic leaflet measuring 20 x 14 mm consistent with endocarditis (yellow arrow).\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-1454220/v1/ede21cc9d7b10ebacce4fc5b.png"},{"id":19336188,"identity":"8fc164db-3e93-4b5d-bea4-f17de0af3f89","added_by":"auto","created_at":"2022-03-17 16:22:15","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":251765,"visible":true,"origin":"","legend":"\u003cp\u003eFundus photography taken six weeks after initial presentation shows a complete resolution of retinal hemorrhages and multifocal retinal lesions, without visible scarring.\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-1454220/v1/5574848c06479e4f320a3404.png"},{"id":19336427,"identity":"62475443-d5e4-48c1-9ef8-10dc1a49ae72","added_by":"auto","created_at":"2022-03-17 16:25:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":449122,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1454220/v1/ec2ca5de-dc88-406d-b7a2-caf59c4df75a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Acute multifocal retinitis in a patient with Q fever (Coxiella Burnetii infection) with endocarditis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eQ fever is a worldwide distributed zoonosis caused by \u003cem\u003eC burnetii\u003c/em\u003e, an obligate gram-negative intracellular organism [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It is primarily transmitted to humans through inhalation of aerosols from contaminated soil or animal waste, with cattle, sheep, and goats being the main reservoirs. Incubation period ranges from 2 to 50 days with a median of 18 days [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Most patients remain asymptomatic or develop a nonspecific and self-limiting febrile illness, so that Q fever remains frequently undiagnosed. Endocarditis is the most common and most serious manifestation of chronic Q fever, but other severe acute or chronic complications also have been described including pneumonia, hepatitis, osteomyelitis, endovascular infection, and involvement of the central nervous system [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOcular involvement has rarely been described in the course of Q fever including anterior and posterior uveitis, optic neuropathy, exudative retinal detachment, and abducens palsy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. We herein describe a patient who developed acute multifocal retinitis (AMR) in association with acute \u003cem\u003eC burnetii\u003c/em\u003e infection with endocarditis.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 67-year-old cattle breeder presented to the emergency department with a 2-week history of persistent fever, headache, and floaters in both eyes. On examination, his best-corrected visual acuity was 20/20 in both eyes. There was no relative afferent pupillary defect, and the ocular motility examination was normal for both eyes. Slit-lamp examination showed a quiet anterior chamber and 1\u0026thinsp;+\u0026thinsp;vitreous cells bilaterally. Intraocular pressure was 12 mmHg in both eyes. Fundus examination revealed multiple white spots at the level of the inner retina, measuring 200 to 500 microns, scattered in the posterior pole and midperiphery in both eyes. There also were a few retinal hemorrhages, with some them having a white center. A flat, well-circumscribed chorioretinal lesion associating atrophic and hyperpigmented areas was seen along the superotemporal vascular arcade in the left eye (LE) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFA showed a masking effect from retinal hemorrhages, a slight hypofluorescence of retinal infiltrates without late staining, and peripheral retinal vascular leakage \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSwept source-OCT scan (Topcon, DRI triton) through a retinal infiltrate in the LE revealed a focal area of retinal hyperreflective thickening extending from the retinal nerve fiber layer to the outer retinal layers, with sparing of the retinal pigment epithelium and choroid. There also was a band-like hyper-reflective area in the middle retina consistent with paramacular acute middle maculopathy (PAMM) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eCardiac examination showed a diastolic decrescendo murmur. TTE showed a mobile echodensity on the anterior aortic leaflet measuring 20 x 14 mm consistent with a diagnosis of endocarditis \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eRepeated blood cultures were negative. A lumbar puncture was performed revealing an aseptic meningitis with increased lymphocyte and protein levels. Laboratory testing was negative for bartonellosis, rickettsial infection, syphilis, and tuberculosis.\u003c/p\u003e \u003cp\u003eThe diagnosis of acute Q fever was made on the basis of SERION ELISA results with positive \u003cem\u003eC burnetii\u003c/em\u003e phase II IgM and increase in \u003cem\u003eIgG titers\u003c/em\u003e from 60 IU/ml to 255 IU/ml on paired serum samples collected 2 weeks apart. The patient was treated with doxycycline 100 mg twice a day for 18 months.\u003c/p\u003e \u003cp\u003eSix weeks after initial presentation, the patient reported the disappearance of floaters. Fundus examination showed a complete resolution of retinal hemorrhages and multifocal retinal lesions, with no residual chorioretinal scars \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Sequential TTE over a two-month follow-up period showed gradual regression of the endocardial vegetation.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best our knowledge, our report is the first to describe the association of AMR with a serologically proven systemic \u003cem\u003eC burnetii\u003c/em\u003e infection. AMR, previously termed acute multifocal inner retinitis, has been considered to be often idiopathic, but several infectious etiologies have been recognized including cat scratch disease, rickettsial infection, and syphilis [\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Recent data from Tunisia show rickettsial disease, including rickettsia conorii and rickettsia typhi, to be the most common cause of AMR [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In the present case, serological testing showed negative results for rickettsial infection and also for cat scratch disease and syphilis. The presence of an associated blood-culture negative endocarditis in a patient with a history of animal contact raised our suspicion of Q fever. The diagnosis was confirmed by the detection of high titers of anti- \u003cem\u003eC burnetii antibodies\u003c/em\u003e and the patient accordingly was treated with oral doxycycline.\u003c/p\u003e \u003cp\u003eThe ocular disease pattern of our patient conformed to most of the previously reported features of AMR, especially with regard to the systemic febrile illness, minimal vision impairment, characteristic multiple inner retinitis spots associated with mild vitritis, and benign and self-limiting clinical course.\u003c/p\u003e \u003cp\u003eEndocarditis has been considered as an almost exclusive complication of chronic Q fever. Our findings, consistent with previous recent data, show that acute endocarditis, readily detectable with TTE, can affect a sizable subset of patients with acute Q fever [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Therefore, early diagnosis of Q fever and associated endocardial involvement is of utmost importance for prompt initiation of antibiotic treatment to prevent persistent endocarditis and related morbidity and mortality.\u003c/p\u003e \u003cp\u003eMultifocal superficial retinal infiltrates associated with Q fever may result from intraretinal multiplication of \u003cem\u003eC burnetii\u003c/em\u003e, or from immune-mediated response to bacterial antigens caused by the deposition of immune complexes, inflammatory cells, or antibodies through retinal vessels [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The vascular tropism of \u003cem\u003eC burnetii\u003c/em\u003e also is reflected in our patient in the presence of associated retinal hemorrhages, retinal vascular leakage, and retinal vascular occlusion in the form of PAMM.\u003c/p\u003e \u003cp\u003eThis case shows that \u003cem\u003eC burnetii\u003c/em\u003e infection should be considered in the differential diagnosis of AMR associated with systemic febrile illness. Serological confirmation is required for a definitive diagnosis that could be challenging. A systematic echocardiography is of utmost importance for early detection of disease-related endocarditis and for prompt administration of appropriate antibiotic treatment to improve clinical outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAMR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAcute Multifocal Retinitis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCoxiella\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFluorescein Angiography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLeft Eye\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOptical Coherence Tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePAMM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eParamacular Acute Middle Maculopathy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTTE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTransthoracic Echocardiogram\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate :\u0026nbsp;\u003c/strong\u003eInformed consent was obtained from our patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;:\u003c/strong\u003e Oral and written consent to publication of the case was obtained from the patient. This report does not contain any personal information that could lead to the identification of the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u0026nbsp;:\u003c/strong\u003e The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;:\u003c/strong\u003e None of the authors has any financial/conflicting interests to disclose\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;:\u003c/strong\u003e Authors received no funding\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u0026nbsp;:\u003c/strong\u003e All authors contributed to the study concept and design, and all authors acquired and interpreted study data. AM, FA, MK, SA, HIHA and ABHK collected data. AM, FA, MK and SM drafted the manuscript. RM and MK provided critical manuscript revisions and supervised the study. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;:\u003c/strong\u003e Ministry of Higher Education and Research of Tunisia\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAngelakis E, Raoult D. Q Fever. Vet Microbiol 2010;140:297-309.\u003c/li\u003e\n\u003cli\u003eTodkill D, Fowler T, Hawker JI. Estimating the incubation period of acute Q fever, a systematic review. Epidemiol Infect. 2018;146(6): 665\u0026ndash;72.\u003c/li\u003e\n\u003cli\u003eDerrick EH. \u0026ldquo;Q\u0026rdquo; fever, new fever entity: clinical features, diagnosis and laboratory investigation. Med J Aust 1973;2:281\u0026ndash;299.\u003c/li\u003e\n\u003cli\u003eKazar J (2005) Coxiella burnetii infection. Ann N Y Acad Sci 1063:105\u0026ndash;114.\u003c/li\u003e\n\u003cli\u003eMillion M, Halfon J, Le Lez ML, Drancourt M, Raoult D. Relapsing uveitis and optic neuritis due to chronic Q fever. British journal of ophthalmology. 2011 Jul;95(7):1026-7, 1038-9. doi:10.1136/bjo.2009.169615.\u003c/li\u003e\n\u003cli\u003eJones MR, Cunningham ET Jr (1997) Bartonella henselae-associated AMR in a patient with acquired immunodeficiency syndrome. Retina 17(5):457\u0026ndash;459\u003c/li\u003e\n\u003cli\u003eLukas JR, Egger S, Parschalk B, Stur M (1998) Bilateral small retinal infiltrates during rickettsial infection. Br J Ophthalmol 82:1217\u0026ndash;1218\u003c/li\u003e\n\u003cli\u003eKhairallah M, Ben Yahia S, Toumi A, Jelliti B, Loussaief C, Romdhane FB, Messaoud R, Chakroun M (2009) Ocular manifestations associated with murine typhus. Br J Ophthalmol 93(7):938\u0026ndash;942\u003c/li\u003e\n\u003cli\u003eCunningham ET Jr, Schatz H, McDonald HR, Johnson RN (1997) Acute multifocal retinitis. Am J Ophthalmol 123(3):347\u0026ndash;357\u003c/li\u003e\n\u003cli\u003eKhochtali, S. Gargouri, S. Zina, I. Ksiaa, N. Abroug, S. Zaouali, et al., Acute multifocal retinitis: a retrospective review of 35 cases, J Ophthalmic Inflamm Infect 8 (1) (2018) 18.\u003c/li\u003e\n\u003cli\u003eMillion M, Thuny F, Bardin N, Angelakis E, Edouard S, Bessis S, et al. Antiphospholipid Antibody Syndrome with Valvular Vegetations in Acute Q Fever. Clin Infect Dis.2016; 62:537 \u0026ndash;44.\u003c/li\u003e\n\u003cli\u003eBitsori M, Vergadi E, Germanakis I, Raissaki M, Galanakis E. Case Report: \u0026Alpha; Case of Endocarditis and Embolic Stroke in a Child, Suggestive of Acute Q Fever Infection. Am J Trop Med Hyg. 2020;103(4):1435-1438.\u003c/li\u003e\n\u003cli\u003eMelenotte C, Epelboin L, Million M, Hubert S, Monsec T, Djossou F et al. Acute Q Fever Endocarditis: A Paradigm Shift Following the Systematic Use of Transthoracic Echocardiography During Acute Q Fever. Clin Infect Dis.2019. 13;69(11):1987-1995.\u003c/li\u003e\n\u003cli\u003eCunningham ET Jr, Schatz H, McDonald HR, Johnson RN (1997) Acute multifocal retinitis. Am J Ophthalmol 123(3):347\u0026ndash;357\u003c/li\u003e\n\u003cli\u003eKhairallah M, Ladjimi A, Chakroun M, Messaoud R, Yahia SB, Zaouali S, Romdhane FB, Bouzouaia N (2004) Posterior segment manifestations of Rickettsia conorii infection. Ophthalmology 111(3):529\u0026ndash;534\u003c/li\u003e\n\u003cli\u003eLumio J, Penttinen K, Pettersson T. Q fever in Finland: clinical, immunological and epidemiological findings. Scand J Infect Dis. 1981;13: 17\u0026ndash;21\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-ophthalmic-inflammation-and-infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joii","sideBox":"Learn more about [Journal of Ophthalmic Inflammation and Infection](http://joii-journal.springeropen.com)","snPcode":"12348","submissionUrl":"https://submission.nature.com/new-submission/12348/3","title":"Journal of Ophthalmic Inflammation and Infection","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Acute multifocal retinitis, Acute Q fever, Coxiella burnetii, endocarditis","lastPublishedDoi":"10.21203/rs.3.rs-1454220/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1454220/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eTo report acute multifocal retinitis in association with serologically-proven \u003cem\u003eCoxiella (C) Burnetii\u003c/em\u003e infection (Q fever) with endocarditis. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMaterial and methods\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eA single case report documented with multimodal imaging.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eA 67-year-old cattle breeder presented with a 2-week history of persistent fever, headache, and floaters in both eyes. On examination, his best-corrected visual acuity was 20/20, and there was 1+ vitreous cells in both eyes. Bilateral fundus examination showed multiple small superficial white retinal lesions scattered in the posterior pole and midperiphery associated with a few retinal hemorrhages. These retinal lesions did not stain on fluorescein angiography (FA) and showed focal hyperreflectivity and thickening primarily involving the inner retinal layers on optical coherence tomography (OCT). There also was a band-like hyper-reflective area in the middle retina consistent with paramacular acute middle maculopathy. Transthoracic echocardiogram (TTE) showed a mobile echodensity on the anterior aortic leaflet consistent with a diagnosis of endocarditis. Elisa assays performed on paired serum samples collected 2 weeks apart showed increase in \u003cem\u003eantibodies\u003c/em\u003e against \u003cem\u003eC\u003c/em\u003e burnetii from 60 IU/ml to 255 IU/ml. The patient was treated with doxycycline 100 mg twice a day for 18 months, with subsequent resolution of the endocarditis. \u0026nbsp;Sequential ocular examinations showed gradual resolution of all acute retinal findings without visible scars.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eAcute Q fever, caused by \u003cem\u003eC burnetii\u003c/em\u003e infection, should be considered in the differential diagnosis of acute multifocal retinitis. A systematic cardiac assessment with echocardiography is essential for early diagnosis of associated endocarditis and for prompt administration of appropriate antibiotic treatment to improve clinical outcomes\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e","manuscriptTitle":"Acute multifocal retinitis in a patient with Q fever (Coxiella Burnetii infection) with endocarditis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-03-17 16:22:12","doi":"10.21203/rs.3.rs-1454220/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-04-19T09:01:13+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-04-15T18:10:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"89399f22-3bae-4dc8-9e36-80714e8a8628","date":"2022-03-22T10:25:06+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-03-19T10:23:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-03-15T13:55:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-03-15T13:55:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Ophthalmic Inflammation and Infection","date":"2022-03-15T12:58:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-ophthalmic-inflammation-and-infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joii","sideBox":"Learn more about [Journal of Ophthalmic Inflammation and Infection](http://joii-journal.springeropen.com)","snPcode":"12348","submissionUrl":"https://submission.nature.com/new-submission/12348/3","title":"Journal of Ophthalmic Inflammation and Infection","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4ba16c53-12e9-407e-84bb-aafcb6835773","owner":[],"postedDate":"March 17th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-04-30T10:14:03+00:00","versionOfRecord":[],"versionCreatedAt":"2022-03-17 16:22:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1454220","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1454220","identity":"rs-1454220","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}