<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="case-report" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.148203.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Case Report</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Case Report : Brucella infection of total knee arthroplasty - The first case report in an endemic country!</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: 1 approved with reservations]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Chalbaoui</surname>
                        <given-names>Ines</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Sallem</surname>
                        <given-names>Sahar</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Meddeb</surname>
                        <given-names>Mehdi</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-1253-5163</uri>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Ernandes</surname>
                        <given-names>Helmi</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Software</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-7796-9782</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Abid</surname>
                        <given-names>Leila</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <xref ref-type="aff" rid="a3">3</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Kaoual</surname>
                        <given-names>Salma</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Funding Acquisition</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <xref ref-type="aff" rid="a4">4</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Mzid</surname>
                        <given-names>Ahmed</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Farah</surname>
                        <given-names>Faten</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <xref ref-type="aff" rid="a3">3</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Besbes</surname>
                        <given-names>Sophia</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a4">4</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Mestiri</surname>
                        <given-names>Mondher</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Kooli</surname>
                        <given-names>Ikbel</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Software</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-1771-7038</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>infectious diseases department, Mohamed Kassab Institute of Orthopedics, Ksar Said, Tunisie, Tunisia</aff>
                <aff id="a2">
                    <label>2</label>orthopedic department, Mohamed Kassab Institute of Orthopedics, tunis, Tunisia</aff>
                <aff id="a3">
                    <label>3</label>anatomopathology department, Mohamed Kassab Institute of Orthopedics, tunis, Tunisia</aff>
                <aff id="a4">
                    <label>4</label>microbiology laboratory, Mohamed Kassab Institute of Orthopedics, tunis, Tunisia</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:kooli.ikbel@gmail.com">kooli.ikbel@gmail.com</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>9</day>
                <month>9</month>
                <year>2024</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2024</year>
            </pub-date>
            <volume>13</volume>
            <elocation-id>1028</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>16</day>
                    <month>7</month>
                    <year>2024</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Chalbaoui I et al.</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/13-1028/pdf"/>
            <abstract>
                <p>Prosthetic joint loosening due to Brucella spp. is a rare event. In this report, we describe a rare case of prosthetic infection caused by brucella.</p>
                <p>A 71-year-old woman reported a six-month history of progressing pain in the right prosthetic knee, which had been implanted for arthrosis four years prior to admission, associated with fever. No night sweats were noted.</p>
                <p>On examination, the right knee appeared slightly swollen and painful on mobilization, and the surgical wound was normal.</p>
                <p>Blood tests showed increased C-Reactive Protein (CRP) (34mg/L) and erythrocyte sedimentation rate (ESR) (34mm/hr).</p>
                <p>A CT scan of her right knee was performed, showing loosening of the prosthesis, joint effusion, and osteolysis in contact with the internal tibial component measuring 16mm maximum with bone remodeling of the epiphysis and metaphysis regions.</p>
                <p>Rose Bengal test was positive for brucellosis, a standard brucella tube agglutination test was positive at a titer of 1/80, blood cultures for brucella were negative and a PCR for detection of Mycobacterium tuberculosis was negative. The patient was diagnosed as having Brucella infection of his total knee arthroplasty. Favorable outcome was observed after medical and surgical treatment. We believe this is the first detailed report of Brucella prosthetic infection in the country despite the endemicity of this type of zoonosis.</p>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Brucellosis</kwd>
                <kwd>Knee prosthesis</kwd>
                <kwd>Loosening</kwd>
                <kwd>Antimicrobial therapy.</kwd>
            </kwd-group>
            <funding-group>
                <funding-statement>The author(s) declared that no grants were involved in supporting this work.</funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec id="sec1" sec-type="intro">
            <title>Introduction</title>
            <p>Brucellosis is a zoonotic infection caused by Brucella species. It can be transmitted to humans through consumption of unpasteurized and contaminated milk products or through contact with infected animals. Osteoarticular involvement is the most common focal presentation. Prosthetic joint infections (PJI) caused by Brucella spp. are uncommonly reported in the literature. It is rarely diagnosed because of uncommon symptoms. Diagnosis is usually based on serology, augmented when possible by culture of Brucella organisms from blood, synovial fluid, or bone. In this case report, we describe an infection of a total knee prosthesis caused by Brucella spp.</p>
        </sec>
        <sec id="sec2">
            <title>Case report</title>
            <sec id="sec3" sec-type="methods">
                <title>Methods</title>
                <p>A 71-year-old woman with a personal medical history of hypertension, diabetes, and dyslipidemia, and a history of consumption of unpasteurized dairy products, was admitted to the Infectious Diseases Department of the Orthopedic Institute of Mohamed Kassab (Tunis, Tunisia) in 2020. She reported a six-month history of progressive pain associated with fever in the right prosthetic knee, which had been implanted for arthrosis four years prior to admission. Night sweats were not observed.</p>
                <p>On examination, the right knee appeared slightly swollen and painful upon mobilization, and the surgical wound was normal. The temperature, blood pressure, and pulse rate were within normal ranges.</p>
                <p>Blood tests showed increased C-Reactive Protein (CRP) (34 mg/L) and erythrocyte sedimentation rate (ESR) (34 mm/hr). Leukocyte and platelet counts were within the normal limits.</p>
                <p>A CT scan of her right knee showed loosening of the prosthesis, joint effusion, and osteolysis in contact with the internal tibial component measuring a maximum of 16 mm with bone remodeling of the epiphysis and metaphysis regions.</p>
                <p>Surgical removal of the prosthesis was performed, followed by implantation of a cement spacer. Intraoperative findings showed an anterior collection in the affected knee, containing a serosanguineous fluid. Intraoperative sample culture showed the presence of Brucella spp.</p>
                <p>The Rose Bengal test was positive for brucellosis, a standard Brucella tube agglutination test was positive at a titer of 1/80, blood cultures for Brucella were negative, and PCR for the detection of Mycobacterium tuberculosis was negative.</p>
                <p>Histopathology of the synovium revealed an often-ulcerated synovial epithelium with an abundant fibrin layer. The sub-synoviocyte tissue is largely infiltrated by inflammatory cells, lymphocytes, plasmocytes, epithelioid cells, and multinucleated Langhans and Muller cells (
                    <xref ref-type="fig" rid="f1">Figures 1</xref>, 
                    <xref ref-type="fig" rid="f2">2</xref>). The patient was diagnosed as having Brucella infection of his total knee arthroplasty.</p>
                <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                    <label>Figure 1. </label>
                    <caption>
                        <title>Polymorphic inflammatory cells, lymphocytes, plasmocytes and epithelioid cells (HE &#x00d7; 400).</title>
                    </caption>
                    <graphic id="gr1" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/162485/b02d71e1-614f-4a76-91ef-329f5d612126_figure1.gif"/>
                </fig>
                <fig fig-type="figure" id="f2" orientation="portrait" position="float">
                    <label>Figure 2. </label>
                    <caption>
                        <title>Ulcerative synovitis with granulomatous inflammation (HE &#x00d7; 200).</title>
                    </caption>
                    <graphic id="gr2" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/162485/b02d71e1-614f-4a76-91ef-329f5d612126_figure2.gif"/>
                </fig>
                <p>Combined antimicrobial therapy consisting of doxycycline 200 mg once a day and rifamycin 600 mg twice daily was initiated.</p>
                <p>The patient received 45 days of doxycycline and rifamycin and was switched to a drug regimen containing 2400/480 mg per day of sulfamethoxazole/trimethoprim and 200 mg per day of doxycycline because of hemolytic anemia caused by rifamycin. A total of 7 months of antimicrobial treatment was administered. The clinical symptoms remitted slowly, and the patient underwent a second stage of surgery consisting of replacement of the cement spacer with a new knee prosthesis. No evidence of recurrence was observed at the final follow-up.</p>
            </sec>
        </sec>
        <sec id="sec4" sec-type="discussion">
            <title>Discussion</title>
            <p>Brucellosis remains an endemic infection and burdensome health issue, especially in Tunisia. Strenuous efforts are required to improve the healthcare quality to prevent this type of infection.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>
                </sup>
            </p>
            <p>Brucella spp. are facultative intracellular gram-negative coccobacilli that are non-motile and non-spore-forming. Three species (
                <italic toggle="yes">B. melitensis</italic>, 
                <italic toggle="yes">B. abortus</italic>, and 
                <italic toggle="yes">B. suis</italic>) are important human pathogens, 
                <italic toggle="yes">B. canis</italic> is less important.</p>
            <p>Osteoarticular involvement is common in brucellosis. Spondylitis, sacroiliitis, osteomyelitis, and peripheral arthritis were the most frequently reported forms of brucellosis.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup>
            </p>
            <p>A Tunisian article, published by H. Battikh, A. Berriche, R. Zayoud et al., reported that osteoarticular involvement was the most common complication of brucellosis, occurring in 28.5% of patients (spondylodiscitis in 20 cases and sacroiliitis in 5 cases) in a series of 109 patients.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>
                </sup>
            </p>
            <p>Brucella infection after total joint arthroplasty is rare and difficult to diagnose.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup>
            </p>
            <p>A systematic review of the literature by Kim et al. reported 18 patients who had Brucella infection following total joint arthroplasty (10 cases of hip joint arthroplasty and 8 cases of knee joint prostheses).
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup>
            </p>
            <p>Our case report revealed the first case of Brucella prosthetic joint infection described in Tunisia despite the endemicity of brucellosis in our country.</p>
            <p>The Steckelberg JO article reported that the mean rate of infections in knee and hip joint arthroplasty, between the second and tenth year after surgery, is, respectively, 2.3 and 5.9 per 1000, respectively, every year.
                <sup>
                    <xref ref-type="bibr" rid="ref5">5</xref>
                </sup>
            </p>
            <p>A single swollen and painful prosthetic joint, as observed in our patient, could be the only clinical symptom. The non-specific signs and rarity of this type of infection make the diagnosis very difficult to establish.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>
                </sup>
            </p>
            <p>The median duration from prosthesis implantation to the onset of symptoms was 3.9 years in a systematic review of literature by Kim et al.
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup> We report a similar duration in our case. The onset of symptomatology was four years after prosthesis implantation.</p>
            <p>Standard radiography did not always show evidence of prosthetic loosening; CT could help, in certain cases, diagnose prosthetic migration and peri-prosthetic tissue damage (abscess, &#x2026;).
                <sup>
                    <xref ref-type="bibr" rid="ref7">7</xref>
                </sup> In our case, a CT scan was performed, which showed prosthetic loosening, joint effusion, and osteolysis in contact with prosthesis components.</p>
            <p>The diagnosis of Brucella infection following total joint arthroplasty can be established based on symptoms (pain, tenderness, and swelling of the prosthetic joint) in the presence of an antibody titer greater than 1/160 in a tube agglutination test (however, the antibody titer in our case was only 1/80). Definitive diagnosis of this infection is based on isolating Brucella spp. from intraoperative sample culture or blood culture.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup>
                <sup>,</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup>
            </p>
            <p>Routine treatment usually includes anti-microbial therapy and surgery if necessary.</p>
            <p>Anti-Brucella agents are necessary; however, there are no standard regimens regarding the type, dose, and duration of different antibiotics that can be administered to treat this type of infection. Most authors have suggested a minimum duration of antibiotic therapy of 6 weeks.
                <sup>
                    <xref ref-type="bibr" rid="ref8">8</xref>
                </sup>
                <sup>,</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref9">9</xref>
                </sup> In our case, we prolonged the antibiotic treatment because the symptoms remitted slowly (swelling and pain persisted for the first 5 months after surgery).</p>
            <p>Surgical removal of the joint prosthesis is a controversial but usually performed procedure because of the potential risk of relapse of infection. It was performed in 61% of patients who were described in the systematic review of the literature by Kim et al.
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup>
            </p>
        </sec>
        <sec id="sec5" sec-type="conclusion">
            <title>Conclusion</title>
            <p>Brucella infection in total joint arthroplasty is an uncommon type of infection that is extremely difficult to diagnose. It is important for physicians to consider this diagnosis in light of every suspicion of prosthesis infection, especially in endemic areas.</p>
        </sec>
        <sec id="sec6">
            <title>Consent to publish</title>
            <p>The patient was informed and consent to publish clinical data was received for this study. She provided written informed consent to publish this case report.</p>
        </sec>
    </body>
    <back>
        <sec id="sec9" sec-type="data-availability">
            <title>Data availability statement</title>
            <p>No data are associated with this article.</p>
        </sec>
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    </back>
    <sub-article article-type="reviewer-report" id="report333077">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.162485.r333077</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Halstead</surname>
                        <given-names>FD</given-names>
                    </name>
                    <xref ref-type="aff" rid="r333077a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-2833-2926</uri>
                </contrib>
                <aff id="r333077a1">
                    <label>1</label>Wye Valley NHS Trust, Hereford County Hospital, Hereford, UK</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>14</day>
                <month>11</month>
                <year>2024</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Halstead F</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport333077" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.148203.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>This paper is a short summary of a case report of brucella being detected in samples taken from a knee of a patient who had had a total knee replacement four years previously. It is an important topic as this is often an infection that goes undetected for a long time, so it is good to report and educate as much as possible. My own father had undiagnosed brucellosis for 10 years, resulting in replacement knees and ankles, so educating workforce is super-important as often over-looked.</p>
            <p> I feel that some improvements could be made to the paper, as there are parts in the case report which aren&#x2019;t clear to me as a laboratory clinical scientist.</p>
            <p> Here are some suggestions: 
                <list list-type="bullet">
                    <list-item>
                        <p>Remove the exclamation mark from the title as this makes the paper seem frivolous</p>
                    </list-item>
                    <list-item>
                        <p>Abstract 
                            <list list-type="bullet">
                                <list-item>
                                    <p>The whole of the abstract has been lifted from the main body of the case report. Try to rephrase where possible as It can be a bit repetitive for the reader to encounter the same information more than once.</p>
                                </list-item>
                                <list-item>
                                    <p>End of para 1, should read 
                                        <italic>Brucella</italic> spp (or ideally, the actual species if known)</p>
                                </list-item>
                                <list-item>
                                    <p>What do you mean by &#x2026;surgical wound was &#x2018;normal&#x2019;?</p>
                                </list-item>
                                <list-item>
                                    <p>What was the actual rose Bengal result (would be nice to state this as a titer etc?)</p>
                                </list-item>
                                <list-item>
                                    <p>The blood cultures were negative &#x2013; when were they collected and how long were they incubated for?</p>
                                </list-item>
                                <list-item>
                                    <p>Last paragraph should read &#x2018;her&#x2019; and not &#x2018;his&#x2019;.</p>
                                </list-item>
                                <list-item>
                                    <p>What surgical treatment did she have? Revision?</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                    <list-item>
                        <p>Introduction 
                            <list list-type="bullet">
                                <list-item>
                                    <p>Maybe mention occupational exposure?</p>
                                </list-item>
                                <list-item>
                                    <p>Mention global distribution if words allow and a bit more about prevalence in Tunisia?</p>
                                </list-item>
                                <list-item>
                                    <p>Reference needed for &#x2018;Osteoarticular involvement&#x2026;&#x2019; statement. Could also add here that it tends to be mostly the leg joints (knees and ankles) and cervical spine</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                    <list-item>
                        <p>Case report 
                            <list list-type="bullet">
                                <list-item>
                                    <p>Comment as per abstract &#x2013; either change wording of abstract, or this wording as both are the same at present.</p>
                                </list-item>
                                <list-item>
                                    <p>Might be nice to put normal reference ranges for CRP and ESR and state values and ranges for leukocytes and platelets if known.</p>
                                </list-item>
                                <list-item>
                                    <p>At the end of para 5, you write that &#x2018;intraoperative sample culture showed the presence of Brucella spp&#x2019; 
                                        <list list-type="bullet">
                                            <list-item>
                                                <p>It would be nice to expand a bit more on this (e.g. was this a tissue, synovial fluid, how long incubation) and what &#x2018;normal&#x2019; tests you did first on the samples</p>
                                            </list-item>
                                            <list-item>
                                                <p>Was Brucella looked for only because everything else was negative? Or was it based on her exposure history? Or is it routine in Tunisia as levels are high?</p>
                                            </list-item>
                                        </list> </p>
                                </list-item>
                                <list-item>
                                    <p>Para 6 &#x2013; when were blood cultures collected? How long incubated for?</p>
                                </list-item>
                                <list-item>
                                    <p>Para 7 &#x2013; &#x2018;the sub-synoviocyte tissue&#x2026;was&#x2026;(instead of &#x2018;is&#x2019;)&#x2026;&#x2019; Also, need to correct &#x2018;his&#x2019; to &#x2018;her&#x2019;.</p>
                                </list-item>
                                <list-item>
                                    <p>Final paragraph &#x2013; at what point was the new knee put in? When was the final follow up done? And how was recurrence ruled out?</p>
                                </list-item>
                            </list> </p>
                    </list-item>
                    <list-item>
                        <p>Discussion 
                            <list list-type="bullet">
                                <list-item>
                                    <p>The flow of the discussion is a bit messy at present. I would suggest starting with 
                                        <list list-type="bullet">
                                            <list-item>
                                                <p>Info about rates of PJI (e.g. Steckelberg)</p>
                                            </list-item>
                                            <list-item>
                                                <p>Then go on to talk about Brucellosis (the species and burden), then the osteoarticular involvement,</p>
                                            </list-item>
                                            <list-item>
                                                <p>Then the rarity of Brucella PJI</p>
                                            </list-item>
                                            <list-item>
                                                <p>Then a reflection on your case and the learning points</p>
                                            </list-item>
                                        </list> </p>
                                </list-item>
                            </list> </p>
                    </list-item>
                </list>
            </p>
            <p>Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?</p>
            <p>Partly</p>
            <p>Is the case presented with sufficient detail to be useful for other practitioners?</p>
            <p>Yes</p>
            <p>Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?</p>
            <p>Partly</p>
            <p>Is the background of the case&#x2019;s history and progression described in sufficient detail?</p>
            <p>Partly</p>
            <p>Reviewer Expertise:</p>
            <p>Clinical microbiology. Personal experience of delayed and difficult diagnosis of brucellosis which resulted in significant patient morbidity.</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
    </sub-article>
</article>
