Molecular Epidemiology of HCV Infection among Multi-Transfused β-Thalassemia Patients in Eastern India: A Six-Year Observation
, Aritra Biswas 1,†, Sagnik Bakshi 1, Promisree Choudhury 1, Raina Das 1, Shreyasi Nath 1, Prosanto Chowdhury 2, Maitreyee Bhattacharyya 3, Sharmistha Chakraborty 4, Shanta Dutta 1 and Provash Chandra Sadhukhan 1,*Round 1
Reviewer 1 Report
The manuscript was prepared with great care.
Here are notes on the manuscript:
1. the introduction is written interestingly and introduces the reader to the topic well.
2. The aim of the work has been clearly defined.
3. Materials and methods are also clearly defined.
4. Fig. 1 should be of better quality. It is currently illegible.
5. Other results are presented clearly.
6. Discussion - please describe the limitations of the study.
7. Paper could consider the following references:
https://www.mdpi.com/1422-0067/19/12/4070
https://www.mdpi.com/1422-0067/22/18/9677
Author Response
Respected Sir/ Madam,
We sincerely thank the reviewers for their insightful comments and constructive feedback on our manuscript entitled “Molecular Epidemiology of HCV Infection among Multi-Transfused β-Thalassemia Patients in Eastern India: A Six-Year Observation”.
We are trying to reply to each comment point by point.
Response to Reviewer 1:
Point 1: The introduction is written interestingly and introduces the reader to the topic well.
Response 1: We appreciate the reviewer’s comments on the Introduction section.
Point 2: The aim of the work has been clearly defined.
Response 2: We admire the reviewer’s comments.
Point 3: Materials and methods are also clearly defined.
Response 3: We acknowledged the reviewer’s comments and thanks.
Point 4: Fig. 1 should be of better quality. It is currently illegible.
Response 4: We have updated a better-quality high-resolution image for Figure 1 as per the reviewer’s suggestion.
Points 5: Other results are presented clearly.
Response 5: We appreciate your feedback.
Points 6: Discussion - please describe the limitations of the study.
Response 6. Thank you for your suggestion and we have included the limitations of the study in the Discussion section. Please refer to lines 427-438.
Points 7: Paper could consider the following references:
https://www.mdpi.com/1422-0067/19/12/4070
https://www.mdpi.com/1422-0067/22/18/9677
Response 7: We have included these references (reference numbers 14 and 15) in the manuscript as suggested by the reviewer. Please refer to lines 70-73.
Reviewer 2 Report
Major comment:
The study omitted any control samples (age-matched non-thalassemic and non-thalassemic patients attending the hospitals or 10 collaborating transfusion centers (TCs). Could you please release a realistic reason for this?
Minor comments:
· The manuscript title needs to reformat; HCV should be the all higher case, remove the distribution word because already implied in the epidemiology meaning, to be “Molecular Epidemiology of HCV Infection among Multi-Transfused β-Thalassemia Patients in Eastern India: A Six Years Observation”
· Also in the aims within the abstract: remove the distribution word (lines 17-18).
· Line 43, After leaving the bloodstream, remove this part, as you know the virus did not leave the blood forever. Yes, it enters the liver but it is still in the blood circulation.
· Lines 45-47, sentence “It is extremely important to know the HCV genotype of an infected patient for genotype specific Direct Acting Anti-virals (DAAs) treatment” is not understood at all.
· Lines 52-57; Approximately one-tenth of the world’s thalassemia patients are born in India every year of which approximately 1-3% in southern India and 3-15% in northern India are carriers” Could you please give an explanation for this (in 2-3 sentence” is due to born for thalassemia mother received multiple -transfusion? Or due to the inherited factor.
· Page 3, figure 1a, could you please put a colored map to be more clear for the readership?
· In table 1, is an informative good table, but to increase its value please depart the +ve/-ve, Viremia samples into sub column one for males and the other for females/each age group.
· In table 2, need to be separation as in table 1.
· You can change the word (lower) because it causes confusion in understanding the sound of sentences from lines 252 to 259.
· Your discussion in lines 261-272 is informative but need to add the effect of the menstrual cycle on principal active components specifically in older thalassemia patients, so it is requested to separate the age period in table 1 and 2.
Author Response
Respected Sir/ Madam,
We sincerely thank the reviewers for their insightful comments and constructive feedback on our manuscript entitled “Molecular Epidemiology of HCV Infection among Multi-Transfused β-Thalassemia Patients in Eastern India: A Six-Year Observation”.
Response to Reviewer 2:
Major comment:
Point 1: The study omitted any control samples (age-matched non-thalassemic and non-thalassemic patients attending the hospitals or 10 collaborating transfusion centers (TCs). Could you please release a realistic reason for this?
Response 1: We thank the reviewer for the valuable insight. Our main aim was to study the post-transfusion transmitted HCV infection and its molecular epidemiology and clearance among multi-transfused β-thalassemia patients in West Bengal. As part of the significant treatment option for β-thalassemia patients, regular blood transfusion is required which is the major reason why the patients get infected with HCV. This study is mainly based on the molecular epidemiology of HCV infection and its genomic variability among the said group of the population. We understand that to validate any study, age and sex-matched control and disease groups are required. However, in this study, we were not focusing on or comparing any clinical parameter related to HCV in thalassemic and non-thalassemic individuals. Additionally, it should also be noted that HCV positivity among the low-age non-thalassemic population is quite low and for this study, we have collaborated with different transfusion centers across the districts. Therefore, including age-matched non-thalassemic patients was beyond the scope of this study. However, as per your suggestion, our future study will include age-matched non-thalassemic individuals to investigate any significant correlation between age and sex-matched thalassemic and non-thalassemic individuals in India.
Minor comments:
Point 1: The manuscript title needs to reformat; HCV should be the all-higher case, remove the distribution word because already implied in the epidemiology meaning, to be “Molecular Epidemiology of HCV Infection among Multi-Transfused β-Thalassemia Patients in Eastern India: A Six Year Observation”.
Response 1: We acknowledge the reviewer’s advice and have made all the aforementioned changes in the title as suggested by the reviewer.
Point 2: Also, in the aims within the abstract: remove the distribution word (lines 17-18).
Response 2: We have removed the word “distribution” from the aims. Please refer to revised line numbers 18-19.
Point 3: Line 43, After leaving the bloodstream, remove this part, as you know the virus did not leave the blood forever. Yes, it enters the liver but it is still in the blood circulation.
Response 3: Thank you for your feedback, we have made the necessary changes. Please refer to revised line number 45.
Point 4: Lines 45-47, sentence “It is extremely important to know the HCV genotype of an infected patient for genotype specific Direct Acting Antivirals (DAAs) treatment” is not understood at all.
Response 4: We have added a section explaining the importance of knowing the genotype of the HCV virus for genotype-specific DAAs treatment. Please refer to lines 47-54.
Point 5: Lines 52-57; Approximately one-tenth of the world’s thalassemia patients are born in India every year of which approximately 1-3% in southern India and 3-15% in northern India are carriers” Could you please give an explanation for this (in 2-3sentence” is due to born for thalassemia mother received multiple -transfusion? Or due to the inherited factor.
Response 5: We explain this statement in lines 58-67.
Point 6: Page 3, figure 1a, could you please put a colored map to be clearer for the readership?
Response 6: We have included a color map in the revised manuscript as per the reviewer’s suggestion.
Points 7: In Table 1, is an informative good table, but to increase its value please depart the +ve/-ve, Viremia samples into sub column one for males and the other for females/each age group.
In Table 2, need to be separation as in Table 1.
Response 7: We appreciate the reviewer’s suggestion. We have updated Table 1 and Table 2 in the revised manuscript for the best interpretation of the reviewer’s comment.
Points 8: You can change the word (lower) because it causes confusion in understanding the sound of sentences from lines 252 to 259.
Response 8: We have changed the word as per the reviewer’s suggestion. (Revised lines 363-365)
Points 9: Your discussion in lines 261-272 is informative but need to add the effect of the menstrual cycle on principal active components specifically in older thalassemia patients, so it is requested to separate the age period in Table 1 and 2.
Response 9: We have included an explanation of the effect of menstrual cycles in female thalassemia patients. Please refer to lines 379-388.
Round 2
Reviewer 1 Report
The Authors have addressed all of my concerns.
Reviewer 2 Report
Thank you for your response and increased your manuscript impact.
