Bartonella quintana and Mycobacterium tuberculosis Coinfection in an HIV-infected Patient with Lymphadenitis

Bartonella quintana and Mycobacterium tuberculosis Coinfection in an HIV-infected Patient with Lymphadenitis

Journal of Infection (2003) 46: 244±255 doi:10.1053/jinf.2002.1040 CASE REPORTS Bartonella quintana and Mycobacterium tuberculosis Coinfection in an...

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Journal of Infection (2003) 46: 244±255 doi:10.1053/jinf.2002.1040

CASE REPORTS

Bartonella quintana and Mycobacterium tuberculosis Coinfection in an HIV-infected Patient with Lymphadenitis E. Bernit1, V. Veit1, B. La Scola2, H. Tissot-Dupont2, J. Gachon1, D. Raoult*2 and J. R. HarleÂ1 1

Service de MeÂdecine interne, HoÃpital de la Conception, 13005, Marseille, France and 2Unite des Rickettsies, Faculte de MeÂdecine, CNRS: UPRESA 6020, 13385 Marseille cedex 05, France

Cat scratch disease (CSD) is usually associated with Bartonella henselae infection in patients with a history of cat exposure, but Bartonella quintana may also be a cause of chronic lympadenopathy in patients with cat or flea contact. The lymph node histopathology of CSD and tuberculosis may be indistinguishable. We report herein the first description of lymph node coinfection with B. quintana and M. tuberculosis in a 32-year HIV-infected woman. Culture of lymph node biopsy material on Columbia agar with sheep blood and on human endothelial cells in shell vial allowed us to isolate not only B. quintana, but also M. tuberculosis hominis. # 2003 The British Infection Society. Published by Elsevier Science Ltd. All rights reserved.

Introduction Bartonella quintana and Bartonella henselae have been recognized as the causative agents of opportunistic infections, such as bacillary angiomatosis, peliosis hepatitis and bacteraemia, in patients with acquired immunodeficiency syndrome (AIDS). Moreover, B. quintana, historically the agent of trench fever, has been isolated from urban homeless persons and alcoholics [1]. Although it is usually transmitted by body lice, some patients have had no apparent loose exposure. Cat scratch disease (CSD) is usually associated with B. henselae in patients with a history of cat exposure, but B. quintana may be a cause of chronic lympadenopathy in patients with cat or flea contact [2,3]. Patients with CSD may be misdiagnosed clinically with tuberculosis, and the histopathology of CSD and tuberculosis may be indistinguishable [4]. Human immunodeficiency virus (HIV)-infected patients are at increased risk for both Mycobacterium tuberculosis reactivation and primary infection. Most often, tuberculosis appears before other manifestations of HIV infection. Extrapulmonary tuberculosis is particularly frequent [5]. We report herein a case of lymph node coinfection with B. quintana and M. tuberculosis in a HIV-infected patient.

Clinical Record A 32-year-old woman was admitted in August 1999 for management of supra-clavicular inflammatory lymphadenitis. She was a native Algerian who lived in Marseilles, France, from *Please address all correspondence to: D. Raoult. Tel.: ‡(33) 491 38 55 17; Fax: (33) 491 83 03 90. E-mail address: didier.raoult@medicine. univ-mrs.fr Accepted for publication 0163±4453/03/$30.00

childhood. During the last two years, she had several sexual contacts. There was no history of drug addiction, and no contact with animals. She had no body lice. She had previously been in good health. She was unaware of any family history of tuberculosis, and had a BCG vaccination scar. In July 1999, the patient had noted a new `lump' in the supra-clavicular area. This mass had enlarged over several weeks despite 10-day treatment with doxycycline (200 mg daily) and was mildly tender. On clinical examination, the diameter of the lymph node was 20 mm. She had no fever nor enlargement of the liver, spleen nor other lymph node. A chest X-ray and scan showed no abnormality. She had a mild normocytic anaemia (haemoglobin level, 11.5 g/dl), mild thrombocytosis (platelet count, 450109/l), and the white blood cell count was 7109/ l (polymorphonuclear, 68%; lymphocytes, 26%). Erythrocyte sedimentation rate was elevated at 72 mm/h, C reactive protein at 40 mg/l (normal < 5 mg/l), and fibrinogen at 4.6 g/l (normal range, 2±3,5 mg/l). The liver functions tests showed only elevated gammaGT at 80 UI/l (normal range, 7±45 UI/l). She had a polyclonal hypergammaglobulinemia at 22%. Tuberculin skin test reaction was positive with 20 mm induration. Blood cultures remained sterile. Serological tests for hepatitis A, B, C, syphilis, B. quintana, B. henselae, and Francisella tularensis were negative. Serological tests for EBV, CMV, HSV, and toxoplasmosis showed an acquired immunity. Serological test for HIV 1 was positive. Viral load was 25,178 copies/ml. CD4 lymphocytes were 416/mm3. No acid-fast bacilli were detected in gastric aspirates and urine samples. The patient was referred for surgical resection of the supraclavicular mass. Histological examination revealed large areas of eosinophilic, caseous-like necrosis. There was surrounding granulomatous inflammation containing epithelioid and multinucleate giant cells, polymorphs and lympho cytes. No acidfast bacilli, fungi or bacteria were identified with special stains

# 2003 The British Infection Society. Published by Elsevier Science Ltd. All rights reserved.

Case Reports (Gram, Periodic Acid Shiff, Gomori±Grocott, Ziehl±Neelsen, methamin silver and Warthin-Starry). Bacteria were not detected by immunohistochemistry using a previously described procedure [6] with both anti-B. quintana and anti-B. henselae antibodies. Lymph node material was inoculated onto Columbia sheep blood agar plates and shell vials for culture of Bartonella sp. as described previously [7]. These procedures allowed isolation of 2 micro-organisms, B. quintana and M. tuberculosis hominis. Molecular detection of Bartonella spp. PCR performed on lymph node sample as previously described [7] was negative. The patient was treated with isoniazid (300 mg daily), rifampin (900 mg daily), ethambutol (1200 mg daily) and pyrazinamide (2000 mg daily) for 3 months and then isoniazid (300 mg daily), rifampin (900 mg daily) for a further 6 months. Antiretroviral treatment consisted of Zidovudine (600 mg daily) and Lamivudine (300 mg daily). Blood samples inoculated onto 5% sheep blood agar and onto a human endothelial cell line (ECV 304) as previously reported [7] remained negative throughout the 12-months follow-up. After 1 year she remains well and there was no relapse.

Discussion We report here the discovery of 3 infections in the same time in a young female patient hospitalized for regional lymphadenitis. We did not obtain any history of exposure for tuberculosis nor B. quintana infection, but she had several possible sexual exposures to HIV infection. The patient lived in hygienic conditions and had no evidence of infestation by body lice. She had no contact with cats nor fleas. Lymphadenitis is the most frequent form of extrapulmonary tuberculosis. In HIV-negative persons, it is usually unilateral and cervical in location [8]. In individuals with AIDS, tuberculous lymphadenitis is almost always multifocal and associated with systemic symptoms such as fever, weight loss, and evidence of tuberculosis elsewhere [5]. Our patient had a CD4 lymphocyte count of 416/mm3, without important immunosuppression, that may explain her limited illness. In contrast to non HIV-infected persons, findings on both cytology and histology are less specific in HIV-infected persons [9]. In this case, it was not possible to differentiate between CSD and mycobacteriosis on the basis of clinical manifestations and histological examination. However, cultures onto Columbia agar with sheep blood and onto human endothelial cells in shell vial allowed us to isolate not only B. quintana, but M. tuberculosis hominis too. P.-E. Fournier recently reported isolation of Mycobacteria from clinical samples using the centrifugation-shell vial technique [4]. Of 256 lymph node biopsies from patients suspected to have CSD, shell vial culture isolated Mycobacteria sp. in seven cases. Histological features in these seven highly suggestive of tuberculosis, but none of them demonstrated mycobacteria by Ziehl±Neelsen acid-fast staining. The centrifugation-shell vial system is a versatile cell culture technique for the culture of viruses, and many facultative or strictly intracellular bacteria. In the reference laboratory for rickettsial diseases, this technique has been routinely and successfully applied to isolation of the pathogens from lymph node biopsies as Bartonella spp. [10] and more recently, Francisella tularensis [11], Mycobacteria spp. [4], and Chlamydia spp. [12]. Even in AIDS patients, the presence of lymphadenopathies was more often found to be associated with B. henselae infection

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(60%) than with B. quintana infection (4%) [6]. To our knowledge, only two cases of B. quintana chronic adenomegaly, one peripheral [3] and one mediastinal [2] have been reported in either immunocompetent or immunosuppressed patients, though B. quintana is rarely considered as an etiological agent and may not be sought. In the two reported cases, there were close contacts with cats. However, B. quintana has never been isolated from cats. No reservoir other than man has been demonstrated. As with our patient, both patients lived in hygienic conditions and had no evidence of infestation by body lice. The epidemiology of B. quintana infection has yet to be determined. In both previous reports, chronic adenopathy was due to granulomatous inflammation without caseation, and B. quintana was isolated from blood and bone marrow, and was also detected by PCR of 16S rRNA [2] in lymph node. In both patients, B. quintana-speciftc antibodies were negative. Serological tests for B. quintana can give false-negative results, especially in immunocompromised patients [2,6]. Both patients were successfully treated by aminoglycosides. There is no consensus regarding the optimum antibiotic treatment of Bartonella infections. In our case, we isolated B. quintana after 10 days of treatment with doxycycline. Regnery et al. [13] reported a case of a an HIV-infected patient with bacillary angiomatosis who relapsed after a 4-week course of therapy with doxycycline, but was cured after a further 8-week treatment with the same drug. Duration of the therapy with tetracyclines and macrolides is critical. Rifampicin is also active against Bartonella spp. [14]. Prolonged therapy in treatment for tuberculosis, as well as susceptibility of the bacteria to rifampicin, may explain the absence of relapse after stopping therapy. Coinfection in immunosuppressed persons is rarely reported, although recurrent and polymicrobial infection are frequently seen in HIV-infected patients. Recently, a case of consecutive B. henselae and Rhodococcus equi bacteremia during acute leukemia was reported in a neutropenic patient [15]. Moreover, coinfection with multiple tick-borne pathogens, in particular Bartonella sp. has been reported in dogs and humans [16]. To our knowledge, there has been no case of isolated lymphadenopathy with bacterial coinfection previously reported in medical literature.

Conclusion We report herein the first description of coinfection with B. quintana and M. tuberculosis hominis in lymphadenitis in HIVinfected person. Both infections seemed to be limited to a peripheral lymph node, without symptoms of disseminated illness. There was no relapse after prolonged treatment for tuberculosis B. quintana is not only associated with trench fever, bacillary angiomatosis and endocarditis, but has also been isolated in granulomatous lymphadenopathy among immunocompetent and immunocompromised patients.

Acknowledgment The authors thank H. Lepidi1 for histological examination of clinical material.

References 1 Brouqui P, La Scola B, Roux V, Raoult D. Chronic Bartonella quintana bacteremia in homeless patients. N Engl J Med 1999; 340: 184±189.

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2 Drancourt M, Moal V, Brunet P, Dussol B, Berland Y, Raoult D. Bartonella quintana infection in a seronegative hemodialized patient. JCM 1996; 34: 1158±1160. 3 Raoult D, Drancourt M, Carta A, Gastaut JA. Bartonella (Rochalimaea) quintana isolation in patient with chronic adenopathy, lymphopenia, and a cat. Lancet 1994; 343: 977. 4 Fournier P-E, Drancourt M, Lepidi H, Gevaudant M-J, Raoult D. Isolation of Mycobacteria from clinical samples using the centrifugation-shell vial technique. Eur J Microbiol Infect Dis 2000; 19: 69±70. 5 Campbell IA. The treatment of superficial tuberculous lymphadenitis. Tubercle 1990; 71: 1±3. 6 Gasquet S, Maurin M, Brouqui P, Lepidi H, Raoult D. Bacillary angiomatosis in immunocompromised patients. AIDS 1998; 12: 1793±1803. 7 La Scola B, Raoult D. Culture of Bartonella quintana and Bartonella henselae from human samples: a 5-year experience (1993 to 1998). JCM 1999; 37: 1899±1905. 8 Summers GD, Mc Nicol MW. Tuberculosis of superficial lymph nodes. Br J Dis Chest 1980; 74: 369±373. 9 Schriner KA, Mathisen GE, Goetz MB. Comparison of mycobacterial lymphadenitis among persons infected with human immunodeficiency virus and seronegative controls. Clin Infect Dis 1992; 15: 601±605. 10 Raoult D, Fournier P-E, Drancourt M, et al. Diagnosis of 22 new cases of Bartonella endocarditis. Ann Intern Medl 1996; 125: 646±652.

11 Fournier P-E, Bernabeu L, Schubert B, Mutillod M, Roux V, Raoult D. Isolation of Francisella tularensis by centrifugation of shell vial cell cultures from multiple liver and lung abscesses. JCM 1998; 36: 2782±2783. 12 Maurin M, Raoult D. Isolation in endothelial cell cultures of Chlamydia trachomatis LGV (serovar L2) from a lymph node of a patient with suspected cat scratch disease. JCM 2000; 38: 2062±2064. 13 Regnery RL, Anderson BE, Clarridge JE et al. Characterization of a novel Rochalimaea species, R. henselae sp. nov., isolated from blood of a febrile human immunodeficiency virus positive patient. JCM 1992; 30: 265±274. 14 Maurin M, Raoult D. Antimicrobial susceptibility of Rochalimaea quintana, Rochalimaea vinsonii, and the newly recognized Rochalimaea henselae. J Antimicrob Chemother 1993; 32: 587±594 15 Lortholary O, Mainardi JL, La Scola B, Gallais V, Frenaux P, Casassus P. Consecutive bacillary angiomatosis and Rhodococcus equi bacteremia during acute leukemia: zoonoses may cause fever in neutropenic patients. Clin Microbiol Infect 2000; 6: 334± 336. 16 Breitschwerdt EB, Atkins CE, Brown TT, Kordick DL, Snyder PS. Bartonella vinsonii subsp. berkolfii and related members of the alpha subdivision of the proteobacteria in dogs with cardiac arrhythmias, endocarditis or myocarditis. JCM 1999; 37: 3618±3626.

doi:10.1053/jinf.2002.1061

Urogenital Infection by Mycobacterium bovis Relapsing after 50 years K. E. Lewis1, M. G. Lucas2, R. Smith3 and N. K. Harrison*1 1

Respiratory Unit; 2Department of Urology, Morriston Hospital, Swansea, Wales, UK and 3CDSC Wales, Abdon House, Wedal Road, Cardiff, CF4 3QX

A 64-year-old man was referred to chest clinic after presenting initially with painless haematuria. Bladder biopsies showed granulomatous inflammation and subsequent urine cultures grew Mycobacterium bovis. He had been treated empirically for genito-urinary tuberculosis twice previously and on both occasions his haematuria ceased. Although the early hospital notes have been destroyed we believe this represents a very late and recurrent relapse of cystitis due to M. bovis.# 2003 The British Infection Society. Published by Elsevier Science Ltd. All rights reserved.

Case History A 64-year-old man presented to the Urology Clinic with three episodes of painless, macroscopic haematuria. He had no other symptoms and was otherwise well. Examination and routine *Please address all correspondence to: Dr N. K. Harrison, Respiratory Unit, Morriston Hospital, Swansea, SA6 6NL. Tel.: 01792 703213; Fax: 01792 703845; E-mail address: [email protected] (N. K. Harrison).

blood tests were normal. A mid stream urine sample contained a few red blood cells but no white blood cells and no organisms. Early morning urine samples were cultured for mycobacteria. Excretion urography showed areas of speckled calcification overlying the mid pole of the left and upper-mid pole of the right kidneys. Following contrast, the upper pole of the right kidney did not enhance and appeared atrophic (Fig. 1). There was no evidence of hydronephrosis or infundibular stenosis. The ureters and bladder outlined normally. A cystoscopy showed small multiple erythematous lesions throughout the posterior bladder wall but not in the trigone as one would