Cervical Lymphadenitis Caused by Mycobacterium Genavense in a Healthy Child

Since the first description of a fatal infection with Mycobacterium genavense in an AIDS patient,1 this nontuberculous Mycobacterium has been identified as a pathogen responsible for more than 10% of disseminated nontuberculous mycobacterial infections in patients with human immunodeficiency virus infection.2 It has been reported in Europe, Australia, Canada and the US (reviewed in References 2 and 3) and is thus considered to be a widespread microorganism.3 However, reports of M. genavense infection in immunocompetent patients have not yet been published. Our description of cervical lymphadenitis caused by M. genavense in a previously healthy 4-year-old girl suggests that the pathogenesis of this microorganism is similar to that of other nontuberculous mycobacteria and that it should be added to the most recent lists4 of the few nontuberculous mycobacteria responsible for disease in healthy children. Case report. A 4-year-old previously healthy girl was referred for evaluation of an enlarged (3- by 4-cm) painless superficial lymph node of the left cervical area. The lump had appeared insidiously and did not resolve after two courses of antibiotics (cefaclor and amoxicillin-clavulanate). The child, who had been immunized with Bacillus Calmette-Guérin at birth, had not been exposed to any known case of tuberculosis. Physical examination was otherwise negative. A tuberculin skin test was performed and resulted in a <10-mm induration. A chest radiogram was normal. The involved node was removed surgically for diagnosis, with the presumption of a nontuberculous mycobacterial lymphadenitis. No microorganisms were seen by direct examination (Gram, Ziehl and auramine stains) of cheesy material, and aerobic and anaerobic bacterial cultures remained negative. Histologic examination revealed a granulomatous lymphadenitis with multiple microabscesses scattered throughout the node. Culture in liquid broth (Bactec®) was positive after 14 weeks of incubation. Nucleic acids extracted from the culture were amplified by PCR,5 yielding the characteristic sequence of M. genavense. The identification of a microorganism previously reported only in immunocompromised patients led to evaluation of the child's immune function which was normal for all indices tested, including antibody responses to previously administered vaccine antigens. Serologic screening for HIV infection was negative. Discussion. Among the many nontuberculous mycobacteria found in the environment, only a few have been found to be responsible for human disease in either previously healthy or immunocompromised individuals. These microorganisms are responsible for distinct syndromes, among which laterocervical lymphadenitis is the most frequent in children.6, 7 These cases present common characteristics6, 7: young age; absence of pain and insidiousness of the infectious process; histopathology, i.e. granulomatous lymphadenitis with occasional acid-fast bacilli; and successful treatment by surgical excision. We report here the case of a young girl with all these characteristics. However, laboratory investigation formally identified the responsible Mycobacterium as M. genavense, a microorganism previously identified only in infected patients with AIDS. M. genavense was identified only a few years ago1 as a pathogen responsible for disseminated infection in HIV-infected patients, most of whom had a chronic illness characterized by fever, diarrhea and massive weight loss.5 Because it does not grow on solid media, identification of M. genavense relies on DNA amplification with primers complementary to bacterial 16S ribosomal RNA.5 Since the initial report and the subsequent descriptions of the laboratory methods required for its proper identification,8M. genavense has been reported by many groups as a pathogen that appears to induce disease patterns very similar to those induced by Mycobacterium avium-intracellulare complex in patients with advanced HIV disease and severe immunosuppression. Although M. genavense has been reported only in humans and pet birds,9 its occurrence in HIV-infected patients from three different continents suggests that it is a widespread microorganism. Its pathogenic mechanisms, however, have not yet been fully elucidated. Disseminated infections reported in severely immunosuppressed patients could represent reactivation of a previously acquired infection, as seen with other mycobacteria. An initial step involving colonization of the gastrointestinal tract was postulated in view of (1) the frequent and severe involvement of the gastrointestinal tract in M. genavense infection in HIV-infected patients and (2) the presence of M. genavense in feces of two HIV-infected patients without disseminated mycobacterial infection.2 The identification of M. genavense in an immunodeficient HIV-negative child with abdominal pain and enlarged abdominal lymph nodes2 and the recent detection of M. genavense-specific DNA in intestinal biopsies from two of nine individuals not infected with HIV10 are also in favor of initial gastrointestinal colonization. Invasive infection in young children with AIDS11, 12 suggested that exposure could occur early in life. This report of a M. genavense laterocervical lymphadenitis in a healthy young child sheds additional light on the pathogenetic mechanisms of this recently described Mycobacterium. Nontuberculous lymphadenitis of young children is considered a primary infection after early exposure to environmental infectious agents. This report indicates that the organism which exists freely in the environment9 may be acquired via the oropharynx and colonize the gastrointestinal tract2, 10 during childhood. Disseminated disease at the time of HIV-induced immunosuppression5 might represent late reactivation rather than primary infection. Understanding that the identification of M. genavense lymphadenitis in an otherwise healthy child does not imply the existence of a yet undetected congenital or acquired immune deficiency thus allows not to perform extensive immunologic investigations likely to be negative. Culture-proved mycobacterial lymphadenitis of children is mainly caused by M. avium-intracellulare complex (65 to 80%) and Mycobacterium scrofulaceum (10 to 20%), whereas only 10% are caused by Mycobacterium tuberculosis.4, 13 This distribution could, however, reflect not only the prevalence of each pathogen in the environment and its pathogenicity but also their relative capacity to grow under routine culture conditions. There are indeed many cases of cervical lymphadenitis where clinical features, histopathologic findings and/or initial detection of acid-fast bacilli by direct examination lead to the diagnosis of presumed mycobacterial infection but where routine cultures fail to grow. As has been the case for mycobacterial infections in HIV-infected patients, true estimation of the proportion of cervical lymphadenitis caused by fastidious mycobacteria such as M. genavense in children will require the use of novel diagnostic techniques. DNA amplification using specific primers,5 which is required for formal species identification, must be applied after prolonged culture in liquid medium (Bactec®). Importantly the identification of M. genavense would not have been achieved in our case as late as 10 weeks after initiation of culture. PCR-based detection of mycobacteria directly from frozen tissues, thus circumventing the need for prolonged culture, has been described5 but is as yet too complicated for routine use. We conclude that M. genavense should be added to the list of the few nontuberculous mycobacteria responsible for disease in immunocompetent patients and that prolonged culture in liquid medium followed by DNA-based analysis of positive cultures should become routine if a true estimation of the prevalence of mycobacteria species is to be established. Vincent Liberek, M.D.; Claudio Soravia, M.D.; Béatrice Ninet; Bernard Hirschel, M.D.; Claire-Anne Siegrist, M.D.