INT J TUBERC LUNG DIS 16(3):287 © 2012 The Union http://dx.doi.org/10.5588/ijtld.12.0061 EDITORIAL Relative reproductive fitness of the W-Beijing genotype ASSOCIATED in many countries with (multi-)drug resistance (MDR), the Mycobacterium tuberculosis W-Beijing genotype has been implicated in outbreaks, and there are indications that it is spreading across the world. 1,2 This has been interpreted as indirect evi- dence for increased reproductive ftness (i.e., the po- tential for an infectious tuberculosis [TB] case to cause secondary cases) of W-Beijing strains relative to other strains. There is little direct evidence for such increased relative reproductive ftness (RRF), e.g., increased clustering of Mycobacterium tuberculosis DNA fngerprints of W-Beijing strains compared to other strains in population-based studies. To avoid bias, such studies need to collect strains from well- defned populations over an extended period. 3 In this issue, Wang et al. report on such a study con- ducted over a period of 12 months in two rural coun- ties in Eastern China using insertion sequence (IS) 6110 restriction fragment length polymorphism (RFLP) typing as the fngerprinting method. 4 Of 351 patients, 243 were infected with W-Beijing strains and 108 with non-W-Beijing strains. The proportion of clustering (32% overall) was associated with MDR (adjusted odds ratio [aOR] 4.7, P < 0.01). Together with the high proportion of patients with a history of previous TB treatment (27%), this indicates ongoing transmis- sion from patients with inadequately treated MDR- TB. However, independently of MDR-TB, the pro- portion of clustering was also strongly increased for W-Beijing genotype infections (aOR 7.8, P < 0.01), indeed suggesting an increased RRF for W-Beijing strains. The study had a short observation period, patients may have been missed due to diagnosis in hospitals or the private sector and the two counties were not adjacent. Resistance patterns other than MDR were not adjusted for, nor were differences in contact with infectious TB patients (e.g., hospitalisation, impris- onment). Each of these limitations may have resulted in an overestimation of the association between clus- tering and genotype. 3 This fnding nonetheless calls for an explanation. Studies in animals and human macrophages suggest that W-Beijing strains induce less infammatory im- mune response and are more virulent than other geno- types. 2 Data on the clinical virulence of the W-Beijing genotype (clinical presentation, response to TB treat- ment) have shown little consistency across studies and populations, 2 and a household-contact study in The Gambia found no genotype-specifc differences in transmission rates. 5 However, as fngerprint cluster data (although often interpreted as merely quantify- ing transmission) represent the combined effect of M. tuberculosis transmission and progression from in- fection to TB disease, the increased RRF of W-Beijing strains may refect increased progression rates rather than increased transmission. Even if the lifetime risk of progression were not increased, a shortened in- cubation period would translate into increased rates of fngerprint clustering if the observation period was only 12 months. Indeed, the Gambian study found signifcantly increased disease progression of W-Beijing strains compared to M. africanum. 5 Combined with an association with MDR-TB, an increased progression rate of W-Beijing strains may over time severely affect the course of the MDR-TB epidemic. There is an urgent need for data to eluci- date the transmission dynamics of M. tuberculosis in relation to strain variation, ideally from well-designed case-contact studies in areas where W-Beijing strains are endemic. Frank Cobelens Department of Global Health and Amsterdam Institute of Global Health and Development Academic Medical Center Amsterdam, The Netherlands e-mail: f.cobelens@aighd.org References 1 European Concerted Action on New Generation Genetic Mark- ers and Techniques for the Epidemiology and Control of Tuber- culosis. Beijing/W genotype Mycobacterium tuberculosis and drug resistance. Emerg Infect Dis 2006; 12: 736–743. 2 Hanekom M, Gey van Pittius N C, McEvoy C, Victor T C, Van Helden P D, Warren R M. Mycobacterium tuberculosis Beijing genotype: a template for success. Tuberculosis (Edinb) 2011; 91: 510–523. 3 Glynn J R, Bauer J, de Boer A S, et al.; European Concerted Ac- tion on Molecular Epidemiology and Control of Tuberculosis. Interpreting DNA fngerprint clusters of Mycobacterium tuber- culosis. Int J Tuberc Lung Dis 1999; 3: 1055–1060. 4 Wang W, Hu Y, Mathema B, Jiang W, Kreiswirth B, Xu B. Re- cent transmission of W-Beijing family Mycobacterium tubercu- losis in rural eastern China. Int J Tuberc Lung Dis 2012; 16: 306–311. 5 De Jong B C, Hill P C, Aiken A, et al. Progression to active tu- berculosis, but not transmission, varies by Mycobacterium tu- berculosis lineage in The Gambia. J Infect Dis 2008; 198: 1037– 1043.