Isolation of Non-Tuberculous Mycobacteria in Children Investigated for Pulmonary Tuberculosis

et al (2006) Isolation of Non-Tuberculous Mycobacteria in Children Investigated for Pulmonary Tuberculosis. PLoS ONE 1(1): e21. doi:10.1371/journal.pone.0000021 Isolation of Non-Tuberculous Mycobacteria in Children Investigated for Pulmonary Tuberculosis Mark Hatherill 0 1 Tony Hawkridge 0 1 Andrew Whitelaw 0 1 Michele Tameris 0 1 Hassan Mahomed 0 1 Sizulu Moyo 0 1 Willem Hanekom 0 1 Gregory Hussey 0 1 0 Academic Editor: Raphael Valdivia, Duke University Medical Center , United States of America 1 1 South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine, University of Cape Town , Cape Town , South Africa , 2 School of Child and Adolescent Health, University of Cape Town , Cape Town , South Africa , 3 Department of Clinical Laboratory Sciences, University of Cape Town , Cape Town , South Africa , 4 National Health Laboratory Service , Cape Town , South Africa Objective. To evaluate the frequency and clinical significance of non-tuberculous mycobacteria (NTM) isolates among children investigated for pulmonary tuberculosis in a rural South African community. Methods. Children were investigated for pulmonary tuberculosis as part of a tuberculosis vaccine surveillance program (2001-2005). The clinical features of children in whom NTM were isolated, from induced sputum or gastric lavage, were compared to those with culture-proven M. tuberculosis. Results. Mycobacterial culture demonstrated 114 NTM isolates from 109 of the 1,732 children investigated, a crude yield of 6% (95% CI 5-7). The comparative yield of positive NTM cultures from gastric lavage was 40% (95% CI 31-50), compared to 67% (95% CI 58-76) from induced sputum. 95% of children with NTM isolates were symptomatic. Two children were HIV-infected. By contrast, M. tuberculosis was isolated in 187 children, a crude yield of 11% (95% CI 9-12). Compared to those with culture-proven M. tuberculosis, children with NTM isolates were less likely to demonstrate acid-fast bacilli on direct smear microscopy (OR 0.19; 95% 0.0-0.76). Children with NTM were older (p,0.0001), and more likely to demonstrate constitutional symptoms (p = 0.001), including fever (p = 0.003) and loss of weight or failure to gain weight (p = 0.04), but less likely to demonstrate a strongly positive tuberculin skin test (p,0.0001) or radiological features consistent with pulmonary tuberculosis (p = 0.04). Discussion. NTM were isolated in 6% of all children investigated for pulmonary tuberculosis and in more than one third of those with a positive mycobacterial culture. NTM may complicate the diagnosis of PTB in regions that lack capacity for mycobacterial species identification. The association of NTM isolates with constitutional symptoms suggestive of host recognition requires further investigation. - INTRODUCTION The diagnosis of pulmonary tuberculosis (PTB) in children is difficult, since disease is often pauci-bacillary [1]. Bacteriological confirmation of M. tuberculosis in children may be possible in fewer than 40% of suspect cases, yet it remains the gold standard in the majority of diagnostic approaches [1]. In practice, highprevalence, resource-limited countries rely on history-taking, tuberculin skin testing, and chest radiography, for investigation of PTB in children [1]. Gastric lavage or induced sputum sampling may not be feasible in many developing country settings, and even if smear microscopy is performed, mycobacterial culture or PCR for species identification may not be available, with the result that a diagnosis of M. tuberculosis will be made if any acid-fast bacilli are detected [1]. Non-tuberculous mycobacteria (NTM) are ubiquitous environmental acid-fast bacilli, which are present in water, soil, and biofilms [2]. Since NTM are resistant to chlorine and biocide disinfection, they frequently contaminate municipal drinking water distribution systems [23]. Although NTM are not obligate pathogens, they share the features of hardiness, hydrophobicity, aerosolization, and intracellular pathogenicity, with M. tuberculosis [2]. The probability of NTM disease is likely to increase with the extent of environmental exposure, particularly in farming communities, with immune susceptibility to opportunistic infection, and with co-existent chronic lung disease such as cystic fribrosis [24]. However, a recent review of the English literature over a period of 70 years describes 43 cases of pulmonary disease caused by NTM in previously well children [5]. In contrast, cervical lymphadenitis is a relatively common mode of presentation in childhood [6]. Increased awareness of NTM, and improved methods of detection, may make it increasingly difficult to distinguish NTM disease from environmental colonization [2]. It might also be difficult to distinguish tuberculous from nontuberculous mycobacterial lung disease on the basis of clinical and radiological features [5]. Detection of non-tuberculous acid-fast bacilli in respiratory se (...truncated)