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Genotyping of Mycobacterium tuberculosis clinical isolates in two cities of Turkey: Description of a new family of genotypes that is phylogeographically specific for Asia Minor

Thierry Zozio, Caroline Allix, Selami Gunal, Zeynep Saribas, Alpaslan Alp, Riza Durmaz, Maryse Fauville-Dufaux, Nalin Rastogi* and Christophe Sola*

BMC Microbiology 2005, 5:44  doi:10.1186/1471-2180-5-44

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Orhan Kaya Koksalan   (2005-09-12 20:21)  Molecular TB Epidemiology Laboratory, Institute for Medical Experimental Research (DETAE), Istanbul University email

In a recent molecular epidemiological study of tuberculosis(TB) performed by Zozio et al(1), a total of 245 Mycobacterium tuberculosis strains from Turkish patients living in Malatya (n=147) and Ankara (n=98), were collected during an interval of seven years (from 1998 to 2004) and were subjected to genotyping.

According to this article(1), the overall TB incidence rate in Turkey was ranged between 26.2 to 26.6 for 100000 inhabitants which in fact, is an underestimate only. Therefore, there must be at least 1578 and 7392 incidental cases of TB in Malatya and Ankara (4000000 inhabitants) along the entire study period, respectively. In other words, this “population-based” study covered less than 1.3% (98/7392) of the expected TB cases in Ankara.

As stated by Murray(2), implicit in the “population-based” approach to molecular epidemiology is the assumption that the results of studies based on the samples are reliable estimates of the parameters of interest in the population from which the sample was drawn. The criteria by which an estimate is judged to be reliable require that it be precise and unbiased, or, in other words, free from both major random and systematic error(3). Small samples usually render parameter estimates imprecise, or more vulnerable to the effects of chance(2).

Keeping the above-mentioned point in mind and based on the results of a long-term, prospective, population-based molecular TB epidemiology project in Istanbul that has been in progress since 2002, which covered 54%(5500 of 10200 strains) of the expected TB cases, we comment the followings;

i. We agree and confirm that LAM-7 family is a predominant and endemic genofamily in Istanbul and the other parts of Turkey,

ii. The small sample size of this study(1), however, resulted in imprecise frequencies; the frequency of ST41 was reported to be 21-25% which is found to be around 15% in our study. The errors grow larger as the study gave its results of MIRU-typing. Namely, the MIRU-pattern of 215125113322 does not account for 58% but 80-85 % of the ST41 spoligotype strains. Similarly the frequency of 214125113322 was reported to be 24%, which is actually about 12%.

iii. The small sample size of the study let the authors miss the great number of DR microevolutions within the LAM-7 family which constitutes a strong evidence for the long-lasting endemicity of the LAM-7 family in Turkey.

iv. The small sample size of the study resulted in overlooking of the other less frequent genotypes which are also specific to Turkey.

v. The study population of this article was entirely Turkish in origin, the language they spoke is Turkish which is branched from the Altaic language family, this means they did not have any relation with the Indo-European language. Therefore, the authors’ claim -even if it may have been taken for true-, that of a hypothetical proto-Indo-European language has existed in Anatolia does not seem to be relevant to the study population. Moreover, as the authors underlined, one should be extremely cautious when making historical inferences, especially when using DNA databases of TB bacilli for this purpose. For our money, mycobacteriologists and TB epidemiologists should be primarily involved with the spread of TB bacilli around the globe and try to specify measures to prevent further transmission. Trying to highlight the human history by using the indirect data produced by DNA databases of TB bacilli should be preferably carried out by the anthropologists and historians, not by the TB epidemiologists and hopefully not by the politicians.

O. Kaya Koksalan,

Molecular TB Epidemiology Laboratory, Institute for Medical Experimental Research (DETAE), Istanbul University, Istanbul Turkey

Zeki Kilicaslan,

Dept of Chest Diseases, Istanbul Medical Faculty, Istanbul University, Istanbul Turkey


1. Zozio T, Allix C, Gunal S, Saribas Z, Alp A, Durmaz R, Fauville-Dufaux M, Rastogi N and Sola C. Genotyping of Mycobacterium tuberculosis clinical isolates in two cities of Turkey: Description of a new family of genotypes that is phylogeographically specific for Asia Minor. BMC Microbiology 2005, 5:44

2. Murray M. Sampling Bias in the Molecular Epidemiology of Tuberculosis. EID 2002, 8:363-369.

3. Hogg RV, Tanis EA. Sampling distribution theory in probability and statistical

inference. 5th edition. Upper Saddle River, NJ: Prentice-Hall.1997: 237-82.

Competing interests

None declared


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