1 Consejería de Sanidad y Consumo, Comunidad de Madrid, Paseo de Recoletos 14, 7a 28001 Madrid, Spain. E-mail: jesus.inigo{at}salud.madrid.org
2 Dirección General de Salud Pública, Consejería de Sanidad de la Comunidad de Madrid, Spain
3 Servicio de Microbiología, Hospital Universitario Doce de Octubre, Madrid, Spain
We appreciate the comments of Borgdorff and colleagues because those comments allow us to clarify some aspects of our article that might have led to misunderstanding some data. Among the 328 culture-positive cases of tuberculosis (TB) of the study population, the epidemiological investigation identified 36 cases which conformed to the definition of recent transmission. Of those, contact investigations identified 16 epidemiologically linked case pairs in which a direction of transmission was specified and fingerprints were available for both isolates (16 source cases and 16 secondary cases). TB transmission was confirmed by restriction fragment length polymorphism (RFLP) typing in all 16 pairs, as stated in our article, and these pairs included 14 source cases, 13 of which were linked to only one secondary case and the other of which was linked to three secondary cases.
As Borgdorff and colleagues correctly mention, these results have been applied to the 20 epidemiologically linked cases without RFLP fingerprints available. Misinterpretation can be originated from the data shown in Table 2. The column which refers to cases with epidemiological evidence of recent transmission should also have included a quotation mark to denote that seven cases were excluded from the Table because RFLP was not available either in the secondary case or the source case. If we had included the 36 cases instead of 29, the odds ratio would have been similar.
Moreover, Borgdorff and colleagues show a theoretical example to reach the conclusion that using capture-recapture in the way we did overestimates the number of cases attributable to recent transmission. However, they have not considered that sensitivity and specificity of epidemiological investigation for identifying recent transmission can be influenced depending on the characteristics of the population studied, e.g. the prevalence of TB, the percentage of foreign-born patients, and differences in case-finding methods. In Spain, a study of contact investigations, including 2148 household contacts, identified 151 secondary cases with active TB.1 This 7% is significantly higher than the 2.4% achieved in San Francisco and mentioned by Borgdorff to illustrate the low sensitivity and limited specificity of epidemiological investigation.
Some studies report the low predictive value of contact investigation for identifying recent transmission of TB, showing that 2930% of epidemiologically linked cases were infected with unrelated strains and that case pairs from the same household were no more likely to have confirmed transmission than those linked elsewhere.2,3 In these studies, case pairs with unconfirmed transmission were more likely to include a foreign-born secondary case. In our experience it is exceptional to find these discordant results. A possible explanation is that in our study population less than 5% of culture-confirmed cases were born out of Spain.
In the absence of a gold standard for recent transmission of TB, the application of capture-recapture analysis in the way we did, assuming the limitations of this analysis, can help us to combine epidemiological information obtained by conventional and molecular methods to quantify the number of cases of recently transmitted TB.
References
1 Vidal R, Miravitlles M, Caylà JA, Torrella M, Martín N, de Gracia J. [Study on contagion in 3071 familial contacts of patients with tuberculosis]. Med Clin (Barc) 1997;108:36165.[ISI][Medline]
2 Behr MA, Hopewell PC, Paz EA, Kawamura LM, Schecter GF, Small PM. Predictive value of contact investigation for identifying recent transmission of Mycobacterium tuberculosis. Am J Respir Crit Care Med 1998;158:46569.
3 Bennett DE, Onorato IM, Ellis BA et al. DNA fingerprinting of Mycobacterium tuberculosis isolates from epidemiologically linked case pairs. Emerg Infect Dis 2002;8:122429.[ISI][Medline]
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