Response to reviewer 2 (John Belisle)
Dear Reviewer,
Thank you very much for all the comments and suggestions which were very important to
improve the manuscript entitled “Effect of anti-tuberculosis drugs on hematological profiles of
tuberculosis patients attending at University of Gondar Hospital, Northwest Ethiopia”. All the
comments were considered important and here below is our point-by point response. We also
want to assure you that all the response documented here are also incorporated in the manuscript.
At this time, we believe that we made the manuscript within the standard requirements of the
BMC hematology.
All the bests!
Baye Gelaw Tarekegn (PhD), corresponding author
Response No 1: The use of healthy controls in the study
At the beginning of this investigation, the hematological parameters of all smear positive TB
patients were determined prior the initiation of the anti-TB drugs. At this point, all the study
subjects were treatment free which is considered as a base line data. Then after completion of the
intensive phase of tuberculosis treatment (2 months), the hematological parameter of each patient
was also determined. Because the aim was to evaluate the effect of the anti-TB drugs on
hematological parameters of TB patients, we did not used health controls as these controls will
not tell us the effect of the anti-TB drugs because they are treatment free.
Response No 1: The effect of host process to clear the bacteria versus the effect of anti-TB
drugs on hematological parameters
In this study, the hematological parameters of TB patients determined prior anti-TB drug
initiation and after completion of the intensive phase of treatment was investigated. We are
assuming that hematological parameters of TB patients would have been remained relatively
similar if patients were not treated with anti-TB drugs because tuberculosis is a chronic disease
whose effect is very gradual. Moreover, the only well known permissive cell that host the TB
bacilli in the lung is the macrophage which have very lower proportion in the peripheral blood on
which hematological parameters are determined. We understand that the immune response after
initiation of anti-TB drugs could have got some strength because the bacillary load is decreasing
as a result of the anti-TB drugs. However, at this point we are expecting that the contribution of
the anti-TB drug in killing the TB bacilli will be by far higher than the immune response and
because of that we evaluated the effect of the anti-TB drugs on hematological profiles in
comparison with that of treatment naïve but the same cases.
Major compulsory concern: demographic data
We used age and sex as demographic characteristics valuable in this study because
hematological parameters reference values are always determined based on age and sex of
individuals. As the aim of this study was to determine the effect of anti-TB drug on
hematological parameters, we considered that demographic characteristics other than age and sex
have only little significance. Hence, we did not consider other demographic characteristics to
compare hematological parameters versus TB treatment. However, the association of age and sex
with that of hematological parameters was analyzed and documented in table 1 in the revised
version of this manuscript.
Minor essential comments
1. Abbreviations in the abstract: The RDW and PDW documented in the abstract are
defined---Thanks.
2. Method to confirm M. tuberculosis infection: This comment was found very important
and we incorporated the method we used to detect the tubercle bacilli in sputum which
was Ziehl-Neelsen staining method---Thank you very much once again.
3. Quality control measures: The quality control measures we used are also re-organized
and all the activities conducted during this study as quality control measures are
documented currently---again many thanks.
4. Terms such as slightly lower and higher and p value=0.000: We used these terms
when we got differences but not statistically significant. However, we tried to minimize
and avoid repetitions. A p-value of 0.000 means strongly associated but p-value of .000 is
actually a mistake and corrected as “0.000”. Currently variables that are significantly
associated are indicated by “‫ ”٭‬in both table 2 and 3.
5. Medical significance of the study findings
The significance of the findings such as reduced Hgb, HCT, platelate, PDW together with
the increased RDW are reflected on the last part of our discussion
6. Editorial error: We tried to edit the manuscript as much as possible and we are hoping
that errors are minimized by now.
7. Burden of acid-fast bacilli versus hematological parameters: We are conscious
enough that tuberculosis may have some effect on hematological parameters and the AFB
score could also contribute to some extent. However, as the tubercle bacillus accumulates
in the lungs and there are very rare or probably no cases of envision of the circulatory
system, the effect of the TB bacilli on hematological parameters by itself can be
considered minimum or negligible. This is evidenced by almost always negative blood
culture taken from TB patients which is reported by different articles. Moreover, we have
known that the lymphatic system is the major route for tubercle bacilli to migrate to
different parts of the host and also to the lungs. Therefore, we are still conscious that the
burden of TB bacilli may not have direct influence on hematological parameters and that
is why we focused on the anti-TB drugs. the most important