PRACTICE | CASES CPD VULNERABLE POPULATIONS

Endocarditis due to quintana, the etiological agent of trench

Carl Boodman MD, Terence Wuerz MD MSc (Epi), Philippe Lagacé-Wiens MD n Cite as: CMAJ 2020 December 7;192:E1723-6. doi: 10.1503/cmaj.201170

CMAJ Podcasts: author interview at www.cmaj.ca/lookup/doi/10.1503/cmaj.201170/tab-related-content

48-year-old man presented to the emergency depart- ment with a 2-day history of pleuritic chest pain and KEY POINTS shortness of breath. His medical history included HIV • , the causal agent of , is infection,A diagnosed 14 years earlier in the context of intraven­ transmitted by body lice (Pediculus humanus var. corporis). ous drug use. Three months previously, he had an undetectable • Although B. quintana is notorious for causing in the First viral load and a CD4 count of 94 cells/mm3 (normal range: 500– World War, outbreaks of trench fever have recently occurred in 1400 cells/mm3) or 0.09 (normal range 0.50–1.40) × 109/L. The urban populations experiencing homelessness. patient adhered to his prescribed antiretroviral regimen (darunavir, • B. quintana causes culture-negative endocarditis and may be ritonavir and abacavir-lamivudine) and prophylaxis against oppor- fatal without antimicrobial and surgical treatment, despite mild tunistic infections (valacyclovir, trimethoprim-sulfamethoxazole symptomatology during chronic bacteremia. Consultation with infectious disease specialists is encouraged. and fluconazole). In addition, the patient had a congenital soli- Because B. quintana evades identification in routine blood tary kidney with normal baseline renal function, alcohol expos­ • cultures, diagnosis of B. quintana requires and explicit ure in utero and alcohol use disorder. He had stopped injecting communication with the microbiology laboratory to incorporate drugs many years earlier. On several occasions over the past measures to specifically recover B. quintana and to arrange 18 months, the patient had sought care for episodes of chest molecular testing. pain and body lice infestation. Although the patient lived in sup- portive housing at the time of presentation, he had lived in a homeless shelter less than a year earlier. mitral valve and severe aortic regurgitation associated with mul- On presentation, the patient’s temperature was 36.7°C, blood tiple smaller vegetations. pressure was 106/65 mm Hg, pulse was 83 beats/min, respiratory Four days after admission, our patient underwent mitral rate was 60 breaths/min and oxygen saturation was 100% on and aortic valve replacement surgery for severe valvular dam- 15 L/min of oxygen. On auscultation, he had a holosystolic mur- age. Pathology results showed 4+ polymorphonuclear cells in mur and an early diastolic decrescendo murmur. Examination of the tissue of both valves; no organisms were seen on Gram the patient’s skin showed hemorrhagic puncta and scabs from staining, and no pathogen growth was detected on aerobic, arthropod bites (Figure 1). There were no peripheral manifesta- anaerobic and fungal cultures. Four blood samples, 2 drawn tions of endocarditis. before antibiotic administration, were culture-negative after Computed tomography of the chest and abdomen showed 5 days of incubation. We were not able to culture any organ- pulmonary emboli, splenic infarcts, and aneur­ ism despite lysis centrifugation and prolonged incubation of ysms of the abdominal aortic branches. A bedside echocardio- 6 weeks. We obtained serologies for Bartonella quintana, gram showed severe mitral regurgitation and a large echogenic ­, and Brucella species as mitral vegetation. Two sets of blood samples were drawn for cul- recommended when there is concern for culture-negative tures before empiric administration of piperacillin-tazobactam endocarditis. Serologies for both Bartonella quintana and and vancomycin for presumptive endocarditis. ­Bartonella henselae showed immunoglobulin G titres greater The patient’s initial tachypnea improved with pain control than 1:8192 (normal range < 1:64),1 while those for Coxiella and and his supplemental oxygen was weaned to 2 L/min. However, Brucella were negative. Results from 16S rRNA sequencing from 10 hours after presentation, the patient became acutely tachy- both valves showed Bartonella quintana genetic material with pneic and hypoxemic, requiring 15 L/min oxygen to maintain 100% homology over 741 base pairs. normal saturation. Because of his worsening respiratory distress, Nine days after admission, we changed the antimicrobial we started mechanical ventilation and transferred him to the therapy to and gentamicin. Because of worsening intensive care unit. A transesophageal echocardiogram showed renal failure, we changed gentamicin to ceftriaxone after severe mitral regurgitation with a 25 × 9 mm vegetation on the 4 days. Ceftriaxone and doxycycline were continued for

© 2020 Joule Inc. or its licensors CMAJ | DECEMBER 7, 2020 | VOLUME 192 | ISSUE 49 E1723 PRACTICE presented inBox1. cmaj.201170/tab-related-content). Asummaryofall4cases is and Appendix2,availableatwww.cmaj.ca/lookup/doi/10.1503/ resources at the same homeless shelter (details in Appendix 1 Winnipeg overa6-monthperiod,allofwhomhadaccessed States and France. homelessness havebeendescribed sincethe1990sinUnited War, buturbanoutbreaksamong individualswhoexperience gen hasbeenassociatedwithtrench feverduringtheFirstWorld severe alcohol use disorderorwhointravenous drugs. 20% amongpeopleexperiencing homelessnesswhohavea E1724 body licefecesintobreaksintheskin. Bartonella quintanaistransmittedviatheinoculationofinfected Discussion discharge. after as an outpatient. He remained well at follow-up3months patient wasdischargedfromhospitalandcompletedtreatment aftersurgery.Twoweeksvalvereplacement, the 6 weeks pressure suchasbeltorsocklines. (patient 1).Notethat,unlikebedbugs,thelesionsdonotfollowareasof on a48-year-oldmanwithendocarditisduetoBartonellaquintana Figure 1:Hemorrhagicpunctatelesionsandscabsfromectoparasitosis Three additional patients with 1,4,5 Seroprevalence for B. quintana B. quintana 2,3 CMAJ Historically,thepatho- Bartonella | DECEMBER 7,2020 were identified in can exceed 1,4,5

| VOLUME 192 leading to the species designation fever” because of its episodic symptom recurrence every 5 days, mycotic aneurysms. cular diseasesuchasculture-negativeendocarditisand minimal symptomsandnofever,itmayalsoleadtoendovas- longed bacteremiaovermanymonthsmaybeassociatedwith ously reportedinCanada. itis, asseenhere. , andelevatedtitresareassociatedwithendocard­ B. quintana itis maybeassociatedwithlowtitres. itis cat scratchdisease,andchronicbacteremiawithoutendocard­ especially withBartonellahenselae,thecausativepathogenof sary toisolatethisorganisminbloodcultures. bacillus. Prolongedincubationofupto6weeksmaybeneces- isafastidious,gram-negative,intraerythrocytic B. quintana Diagnosis associated withfever,headacheandmalaise. Trench fever is a clinical syndrome caused by Clinical presentation freeze–thaw. and improve yield, such as lysis centrifugation or and toperformadditionaltechniquesreleaseintracellular quintana withthemicrobiologylaboratorytoextendincubation tures for 5 days, it is essential to discuss cases of suspected that microbiologylaboratoriesroutinelymaintainbloodcul- teremia andmildsymptomatology. ’s prolongedbac- embolic disease,isconsistentwithB. quintana patient’s indolent presentation, until the development of severe endocarditis.The osis, beforethediagnosisofB. quintana chest painandbodyliceinfestation,alsoknownasectoparasit- gery. rate despitetargetedantimicrobialtherapyandvalvularsur- endocarditisisassociatedwitha10%–12%mortality B. quintana species-level confirmationwhenno valvetissueisobtained.In species-level lensis, whichisnotahumanpathogen. - with thenexthighesthomology (99.03%)wasBartonella senega ficient toachievespeciesdiscrimination. Inthiscase,thespecies 0.8% fromthespecieswith nexthighest16Shomologyissuf- . Adifferenceofgreaterthan other species,includingB. henselae homology withB. quintana sequencing, thevalvulartissueobtainedhereshowed100% ella species may interfere with their identification by 16S Although highlevelsofgeneticsimilaritybetweencertainBarton - endocarditis. provides species-leveldiagnosisofB. quintana about 1monthtoreturn. Microbiology LaboratoryinWinnipeg,theresultsofwhichtake is requestedinCanada,serumsamplesaresenttotheNational with lowertitres. carditis, andchronicinfectionwithoutendocarditisisassociated described. and bonepainlocalizedtotheanteriortibiahavebeen The patientdescribedherehadrepeatedlysoughtcarefor B. quintana B. quintana Molecular testingwith16SrRNAsequencingofvalvulartissue 3,6 We areaware of only 4other cases of 2 Trenchfeverwasoriginallydescribedas“quintan | 8,9 ISSUE 49 infection maybediagnosedwithout molecular Serological testing may show exposure to 6 However, serology is prone to cross-reactivity, However,serologyispronetocross-reactivity, 6,9 Titresover1:800areconsistentwithendo- 5,6,9 7,8 andsubstantialseparationfrom 3,9 . B. quintana 5,9 serology serology WhenB. quintana 3,6,9 B. quintana previ- 3,8,9 6 Splenomegaly Although pro- B. quintana Considering B. B. , PRACTICE ​ - E1725 Patient 4 Patient B. quintana infection (56 d) Ceftriaxone (56 d) Vancomycin (56 d) Doxycycline (14 d) Gentamicin 33 Male hemorrhage Intracranial mycotic (ruptured aneurysm) Mitral None Serology No intervention at meals Received homeless shelter, possible ectoparasitosis community in rural Yes Yes • • • • deficits neurologic Severe and severe (paralysis aphasia) expressive B. quintanaunder- remains likely infection Patient 3 Patient Ceftriaxone (43 d) Ceftriaxone (21 d) Vancomycin (22 d) Daptomycin ISSUE 49 ISSUE 35 Male hemorrhage Intracranial mycotic (ruptured aneurysm) Mitral disease heart Rheumatic Serology artery coiling Cerebral homeless shelter, at Slept possible ectoparasitosis community in rural Yes No • • • deficits Mild neurologic aphasia) (mild expressive | Jackson LA, Spaeh DH, Kippen DA, et al. Seroprevalence to Bartonella quin- tana among patients at a community clinic in downtown Seattle. J Infect Dis 1996;173:1023-6. Ohl ME, Spach DH. Bartonella quintana and urban trench fever. Clin Infect Dis 2000;31:131-5. Infect Lancet homeless. the in Infections P. Brouqui C, Foucault D, Raoult Dis 2001;1:77-84. in species Bartonella to Antibodies al. et RL, Regnery C, Flynn JA, Cormer inner-city intravenous drug users in Baltimore, Md. Arch Intern Med 1996; 156:2491-5.

3. 1. 2. 4. among at-risk populations. therapy to address body lice and other ectoparasite infesta ectoparasite other and lice body address to therapy prevent to considered be should tions References Conclusion B. quintana fever and , transmitted by body lice, causes trench can lead to culture-negative endocarditis among people who experience homelessness. Clinicians should consider Bartonella serology, echocardiography and infectious disease consultation consultation disease infectious and echocardiography serology, when caring for individuals who present unwell with a history of infestation. lice body diagnosed. Seroprevalence, bacteremia surveillance and ecto- parasite studies are needed to understand its true burden among people who experience homelessness. VOLUME 192 VOLUME |

Patient 2 Patient 6 6 Gentamicin (14 d) Gentamicin (42 d) Doxycycline Male Murmur (incidental) Mitral None Serology and 16S from tissue valve replacement Valve homeless shelter at Slept No Yes • recovery Full • 62 testing, testing, However, given However, given 6 DECEMBER 7, 2020 | CMAJ Patient 1* Patient Gentamicin (4 d) Gentamicin (42 d) Ceftriaxone (42 d) Doxycycline Male and Embolization valvulopathy and aortic Mitral None Serology and 16S from tissue valve replacement Valve homeless shelter at Slept No Yes • • • recovery Full 48 In our case, the patient was treated with a regi- 6–8,10 . Considering the rarity of requests for B. quintana Gender syndrome Presenting involvement Valvular disease valvular Previous testing Diagnostic intervention Surgical exposure Possible community rural Links to department Emergency within 3 months presentation admission hospital before therapy Antimicrobial Outcome Age, yr Age, *Patient 1 is the case presented in text. presented 1 is the case *Patient infections among 4 patients in Winnipeg patients among 4 infections quintana 1: Summary Bartonella of Box Characteristic men of ceftriaxone without prolonged aminoglycoside admin- istration, with good clinical outcomes. Further studies are ­necessary to support ceftriaxone and doxycycline regimens without the addition of aminoglycosides. We strongly suggest consultation with infectious disease specialists. As illustrated in our patient, trimethoprim-sulfamethoxazole does not treat or prevent infections with B. quintana. A low threshold to offer

infections due to B. quintana likely remain underdiagnosed. Treatment and prevention Standard treatment of B. quintana bacteremia and endocard­ itis includes a combination of gentamicin and doxycycline. such cases, it is important to confirm possible exposure to bodysuch cases, it is important to confirm possible harbour which cats, to exposure substantial exclude to and lice B. henselaewith that may cause serologic cross-reactivity B. quin- tana Gentamicin is typically administered for 14 days, with doxycy- cline. Doxycycline is continued for 4 weeks in the absence of endocarditis and for at least 6 weeks in cases of endocarditis. The inclusion of gentamicin is associated with improved clin­ ical outcomes and clearance of bacteremia. the risk of gentamicin toxicity, cases have been successfully successfully been have cases toxicity, gentamicin of risk the or doxycycline either and ceftriaxone of regimens treated with rifampin. PRACTICE E1726 6. 7. 5.

North America.AmJTropMedHyg2019;100:1125-9. side oftheEurope–Africangradient:comprehensivereviewcaseswithin Lam JC,FonsecaK,Pabbarajuetal.Bartonellaquintanaendocarditisout- management. EmergInfectDisJ2006;12:217-23. Foucault C,BrouquiP,RaoultD.Bartonellaquintanacharacteristicsandclinical quintanainhomelesspeople.ClinInfectDis1996;23:756-9. Bartonella Brouqui P, Houpikian P, Dupont HT, et al. Survey of the seroprevalence of (Lagacé-Wiens), Winnipeg, Man. (Lagacé-Wiens), Winnipeg,Man. University ofManitoba;SharedHealth ences (Wuerz),MaxRadyCollegeofMedicine, Lagacé-Wiens) andCommunityHealthSci- biology andInfectiousDiseases(Boodman, Medicine andDepartmentsofMedicalMicro- (Boodman, Wuerz),DepartmentofInternal Affiliations: SectionofInfectiousDiseases The authorshaveobtainedpatientconsent. This articlehasbeenpeerreviewed. Competing interests:Nonedeclared. CMAJ | DECEMBER 7,2020 aspects ofthework. lished andagreedtobeaccountableforall gave finalapprovaloftheversiontobepub- ical revisionsbeforesubmission.Allauthors provided essentialmanuscripteditsandcrit- supervision duringthecases.Allauthors Terence Wuerzprovidedclinicaladviceand provided microbiologic support to the case. of theclinicalcase.PhilippeLagacé-Wiens the manuscriptandprovidedspecificdetails the overallconceptionofarticle,drafted Contributors: Carl Boodman contributed to | VOLUME 192 10. 9. 8. ella endocarditis.ArchInternMed2003;163:226-30. Raoult D,FournierP-E,VandeneschF,etal.OutcomeandtreatmentofBarton- homeless patients.NEnglJMed1999;340:184-9. Brouqui P,LascolaB,RouxV,etal.ChronicBartonellaquintanabacteremiain carditis. CanJCardiol2016;32:395.e9-10. Keynan Y,MackenzieL,Lagacé-WiensP.Quintessentialculture-negativeendo- | ISSUE 49 [email protected] [email protected] Philippe Lagacé-Wiens, ​ [email protected]; Correspondence to:CarlBoodman, circumstances. and their resilience in the face of difficult their willingness to participate in this project their patientsforpositiveoutlook, Acknowledgments: Theauthorsthank