Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India

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However, this method has low sensitivity due to suboptimal sampling and techniques. While AFB culture remains a gold standard for diagnosing TB and other mycobacterial infections, its limitations include slow turnaround time, and the requirement for specialized resources and expertise. Neutrophils, monocytes, and lymphocytes are crucial in the pathogenesis of granulomatous inflammation and immune reactions. We investigated the usefulness of the haematological parameters and their ratios, like the Neutrophil to Lymphocyte ratio (NLR) and Monocyte to Lymphocyte ratio (MLR), for diagnosing tuberculosis. Methods We retrospectively grouped 114 patients with fever into those diagnosed with TB and control groups. We obtained their haematological data and calculated their derived ratios. The ratios obtained from the two groups were compared. Their sensitivity and specificity were calculated. Results Haematological parameters like MLR were higher in TB patients than in the control group. Although NLR was not significantly increased, MLR was significantly increased with p values <0.05. These tests had low sensitivity but high specificity. Conclusion Serum NLR and MLR emerge as valuable tools in TB diagnosis. Their simplicity and cost-effectiveness render them particularly suitable for screening and recurrence monitoring in rural and remote settings, thereby mitigating loss to follow-up. 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F1000Research 2025, 13 :747 ( https://doi.org/10.12688/f1000research.150685.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Revised Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] Poorva Bakshi https://orcid.org/0009-0007-0888-1614 1 , Rakshatha Nayak https://orcid.org/0000-0002-7257-1465 1 , Sharada Rai 1 , Shikha Jayasheelan https://orcid.org/0009-0008-2554-7711 1 Poorva Bakshi https://orcid.org/0009-0007-0888-1614 1 , Rakshatha Nayak https://orcid.org/0000-0002-7257-1465 1 , Sharada Rai 1 , Shikha Jayasheelan https://orcid.org/0009-0008-2554-7711 1 PUBLISHED 08 Jan 2025 Author details Author details 1 Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India Poorva Bakshi Roles: Data Curation, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Rakshatha Nayak Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Sharada Rai Roles: Conceptualization, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Shikha Jayasheelan Roles: Conceptualization, Data Curation, Methodology, Supervision, Validation, Visualization, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Manipal Academy of Higher Education gateway. Abstract Background Diagnosis of tuberculosis (TB) in resource-limited countries relies primarily on bacteriological confirmation using Ziehl-Neelsen (ZN) stain on sputum or other representative samples. However, this method has low sensitivity due to suboptimal sampling and techniques. While AFB culture remains a gold standard for diagnosing TB and other mycobacterial infections, its limitations include slow turnaround time, and the requirement for specialized resources and expertise. Neutrophils, monocytes, and lymphocytes are crucial in the pathogenesis of granulomatous inflammation and immune reactions. We investigated the usefulness of the haematological parameters and their ratios, like the Neutrophil to Lymphocyte ratio (NLR) and Monocyte to Lymphocyte ratio (MLR), for diagnosing tuberculosis. Methods We retrospectively grouped 114 patients with fever into those diagnosed with TB and control groups. We obtained their haematological data and calculated their derived ratios. The ratios obtained from the two groups were compared. Their sensitivity and specificity were calculated. Results Haematological parameters like MLR were higher in TB patients than in the control group. Although NLR was not significantly increased, MLR was significantly increased with p values <0.05. These tests had low sensitivity but high specificity. Conclusion Serum NLR and MLR emerge as valuable tools in TB diagnosis. Their simplicity and cost-effectiveness render them particularly suitable for screening and recurrence monitoring in rural and remote settings, thereby mitigating loss to follow-up. READ ALL READ LESS Keywords NLR, MLR, Tuberculosis, Infectious diseases, Hematology Corresponding Author(s) Rakshatha Nayak ( [email protected] ) Close Corresponding author: Rakshatha Nayak Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Bakshi P et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Bakshi P, Nayak R, Rai S and Jayasheelan S. Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.12688/f1000research.150685.2 ) First published: 05 Jul 2024, 13 :747 ( https://doi.org/10.12688/f1000research.150685.1 ) Latest published: 08 Jan 2025, 13 :747 ( https://doi.org/10.12688/f1000research.150685.2 ) Revised Amendments from Version 1 The abstract was revised to include other disadvantages of AFB culture, beyond its sensitivity. An addition regarding the challenges of obtaining sputum from patients without a cough was done in introduction. The study population consisting of patients presenting with fever including both pulmonary and extrapulmonary TB cases are clearly specified in the inclusion criteria under methodology. It is explained how controls were classified as true negatives. We clarified the limitation of excluding TB patients without fever, noting the study's focus on fever as a common symptom in all TB cases. Comorbidities mentioned in the exclusion criteria for patients were further specified. Comparison of haematological parameters between different age groups and sexes were added in the results. The abstract was revised to include other disadvantages of AFB culture, beyond its sensitivity. An addition regarding the challenges of obtaining sputum from patients without a cough was done in introduction. The study population consisting of patients presenting with fever including both pulmonary and extrapulmonary TB cases are clearly specified in the inclusion criteria under methodology. It is explained how controls were classified as true negatives. We clarified the limitation of excluding TB patients without fever, noting the study's focus on fever as a common symptom in all TB cases. Comorbidities mentioned in the exclusion criteria for patients were further specified. Comparison of haematological parameters between different age groups and sexes were added in the results. See the authors' detailed response to the review by Tutik Kusmiati See the authors' detailed response to the review by Sivaporn Gatechompol READ REVIEWER RESPONSES Introduction Tuberculosis (TB) is a chronic disease caused by the bacterium Mycobacterium tuberculosis, which has led to significant mortality and morbidity worldwide. Global statistics indicate that 10 million people have been diagnosed with TB. 1 In particular, India bears the highest burden of TB, with an estimated 26.4 lakh cases. 2 The impact of socioeconomic factors on TB outcomes in India has been well-documented. 3 The most common, rapid, and cost-effective diagnostic method for TB in India is the microscopic detection of Acid-Fast Bacilli (AFB) using Ziehl-Neelsen (ZN) staining. However, this method’s sensitivity decreases when the bacterial load is less than 10,000 bacilli/ml, requiring high-quality and large samples. 4 AFB culture and nucleic acid amplification tests (NAAT), which are more sensitive, are typically conducted in tertiary centers but are limited in rural areas of developing countries due to resource constraints. 5 Moreover, in patients who only produce a small amount of sputum or no sputum at all or in cases of extrapulmonary TB, more interventional methods may be required to obtain adequate samples. Additionally, collection of samples must be done cautiously to avoid contamination, thus demanding technical expertise. While the National Health Mission guidelines suggest diagnosing and treating TB based on high clinical suspicion, studies indicate lower survival rates among patients who receive empirical TB treatment compared to those with laboratory-confirmed TB infection. 4 Despite being curable, late diagnosis, ineffective treatment, and loss of follow-up can result in relapse or the development of multidrug-resistant tuberculosis (MDR-TB) or extensively drug-resistant tuberculosis (XDR-TB). Late detection is primarily due to the unavailability of cost-effective and rapid tests in rural areas, exacerbating the TB burden in India. Loss of follow-up and relapse are often attributed to difficulties in accessing these tests. Timely, accurate, and affordable diagnostics are crucially needed, as delays in diagnosis can worsen outcomes and increase transmission rates. TB is characterized by granulomatous inflammation and caseous necrosis, with neutrophils playing a significant role in its pathogenesis. 6 – 9 Activated macrophages release tumor necrosis factor (TNF) and chemokines, recruiting more monocytes and ultimately leading to the death of the mycobacterium. 10 Hematological parameters such as neutrophils, lymphocytes, and monocytes exhibit variations in TB patients. 11 – 13 In recent years, ratios derived from various hematological parameters have been explored as markers of inflammation in multiple diseases. NLR and MLR have demonstrated both diagnostic and prognostic value in TB. 6 – 17 These tests are simple, rapid, cost-effective, and readily available even in rural areas, promising potential as adjunctive biomarkers for diagnosing and screening clinically suspected TB patients and detecting relapse in patients under follow-up. Methods This is an analytical observational case-control study. The study was conducted at our tertiary hospital in Karnataka state of South India, from June to August 2022. The study included inpatients and outpatients who presented with a fever, had undergone laboratory tests in our institutional hospital to rule out both pulmonary and extrapulmonary tuberculosis, and had adequate clinical data including the presence or absence of history of cough, weight loss etc and radiological findings. All pediatric patients below 18 years, terminally ill patients, patients with known comorbidities like diabetes, sero-positive status and those who were on any treatment were excluded from the study. The sampling process involved two stages. At first, a non-probability, convenience sampling method was employed to identify potential participants based on their presentation with fever and undergoing TB testing. Subsequently, purposive sampling was applied to select participants, strictly meeting the inclusion and exclusion criteria to minimize selection bias and ensure the representation of relevant clinical characteristics within each group. In this study, an effect size of 0.5 was chosen based on prior knowledge or expected differences in the variables under investigation, and a power of 80% (or 0.80) was selected. Kelsey’s formula was employed to calculate the sample size required for each group. This formula incorporates the effect size, power, and significance level to determine the minimum sample size needed to detect a significant difference between groups. A minimum sample size of 55 participants per group was calculated and deemed sufficient to detect the specified effect size with the chosen power level. The patients were divided into a TB group if the patients had a fever and tested positive for TB either by AFB culture, ZN stain, or NAAT and a control group if patients had a fever but tested negative for TB by the above-mentioned methods or by radiology or were positive for other infections by culture. The clinical details were procured from the case files. For the hematologic evaluation, for all groups, the following blood parameters: differential neutrophil, lymphocyte, and monocyte counts, were measured by an automated haematology analyser. The NLR was calculated by dividing the differential neutrophil count by the differential lymphocyte count, and the MLR by dividing the differential monocyte count by the differential lymphocyte count. Data was collected from laboratory software or case files and presented as mean±standard deviation (SD). It was recorded using Microsoft Excel. Statistical Package for the Social Sciences, version 29 software was used for statistical analysis. The T-test was used for continuous variables, and the chi-square test for categorical variables. A p-value of <0.05 was considered statistically significant. Ethics and consent We obtained approval from the Institutional Ethics Committee. (Kasturba Medical College, Mangalore), Reg. No. ECR/541/Inst/KA/2014/RR-20, DHR Reg. No. EC/NEW/INST/2020/742 with Protocol No. IECKMCMLR-11/2021/343. The approval was given on 17 th November 2021. The committee permitted a waiver of consent to participate from the patients as patient details and data were sourced from case files, and tracing the patients proved challenging. Results In total, 114 cases were included in the study, evenly distributed between the TB group (n=57) and the control group (n=57). Key hematologic markers assessed included Neutrophils, Lymphocytes, and Monocytes, with Neutrophil to Lymphocyte Ratio (NLR) and Monocyte to Lymphocyte Ratio (MLR) derived for each participant. 18 No significant differences were observed in any haematological parameters between different age groups or between the two sexes in our study. Differential lymphocyte counts were found to be significantly elevated in TB cases compared to controls (P value=0.048), while MLR showed a significant increase in TB cases compared to controls (P value=0.031). However, no significant differences were observed in the counts of Neutrophils, Monocytes, and NLR between TB cases and controls. To distinguish between TB patients and controls, the cut-off values were established using Receiver Operating Characteristic (ROC) curve analysis. The cut-off value for NLR was set at >5 ( Figure 1 ), while for MLR, it was set at >0.5 ( Figure 2 ). Individually, NLR and MLR exhibited limited sensitivity in predicting TB, but demonstrated better specificity. However, when combining these parameters, there was significant increase in specificity, as shown in Table 1 . 19 Figure 1. ROC curve for NLR. Figure 2. ROC curve for MLR. Table 1. Performance metrics of NLR, MLR, and combined NLR & MLR for predicting tuberculosis. Metrics NLR MLR NLR & MLR Sensitivity % 28.0 38.6 22.8 Specificity % 77.2 78.9 96.5 Positive Predictive Value % 55.2 64.7 86.7 Negative Predictive Value % 51.8 56.3 55.6 Discussion Tuberculosis remains a significant cause of morbidity worldwide, especially in low-income countries, emphasizing the critical need for accessible and cost-effective diagnostic methods. Despite the availability of rapid tests like the NAAT assay, challenges persist, particularly for diagnosing extra-pulmonary, pediatric, and smear-negative TB cases. Conventional methods such as smear tests are outdated, while serological tests lack accuracy. 16 , 17 Our study focused on key hematological parameters including neutrophil count, lymphocyte count, monocyte count, neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR) in patients presenting with fever, comparing those diagnosed with TB to others. Previous research has underscored NLR and MLR as significant markers for TB diagnosis and prognosis. 6 – 16 In our investigation, MLR emerged as a standout parameter, exhibiting a statistically significant increase in TB patients compared to those without TB. This finding underscores the involvement of activated macrophages and monocytes in chronic granulomatous inflammation characteristic of TB. However, contrary to some prior studies, NLR did not demonstrate a significant role in TB diagnosis, possibly due to the involvement of neutrophils in non-granulomatous and acute inflammatory conditions. While NLR and MLR have shown associations with TB disease severity and treatment outcomes in some studies, their predictive value is not universally consistent. 14 – 17 Factors like comorbidities, immune status, and TB strain virulence can influence the relationship between these ratios and clinical outcomes. NLR and MLR can also vary significantly between individuals based on factors like age, sex, and ethnicity and can fluctuate over time due to stress, medications, and physiological changes. 15 While individual hematological parameters showed limited sensitivity, combining MLR and NLR substantially improved sensitivity, specificity, and positive predictive value. This suggests the potential for a combined approach to aid in TB detection. Acknowledged study limitations include, unknown hidden comorbidities, unsuspected infections or immune status, unknown stress factors in both control and cases, and the unknown virulence of the TB strain, potentially introducing variability in laboratory findings. Other limitations include the possibility of selection bias in the patient selection process despite strict adherence to inclusion and exclusion criteria due to a lack of relevant investigations of the desired population. Notably, individuals with TB who did not present with fever were excluded, potentially limiting the study’s representativeness of the TB population. Despite these limitations, our study highlights the importance of utilizing hematological parameters, particularly MLR, in TB diagnosis. While these ratios are non-specific, have inter-individual variation and limited predictive value, limiting their reliability as standalone markers of TB severity or treatment response, combining these ratios with established tests like elevated Erythrocyte Sedimentation Rate (ESR) offers promise for TB screening in resource-limited settings. Conclusion In conclusion, MLR emerges as a promising, cost-effective tool for early TB diagnosis. Utilizing a combined approach with NLR enhances screening efficacy, especially in cases with strong clinical suspicion. Moreover, this combined strategy holds the potential for monitoring patients during follow-up, mitigating relapse risks, and alleviating the TB burden, particularly in underserved regions and rural areas of low-income countries. Variations in study populations, laboratory methods, and analytical techniques contribute to inconsistencies in cutoff thresholds, hindering comparability and generalizability across studies. Therefore this avenue warrants further research to know its hold in clinical implications and also to validate their diagnostic accuracy, prognostic value, and predictive capabilities across diverse patient populations and clinical settings. Data availability statement This project contains the following underlying data: 1. Data Excel sheet for Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India, Figshare: https://doi.org/10.6084/m9.figshare.23684778.v5 18 2. Statistical analysis of Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India, Figshare: https://doi.org/10.6084/m9.figshare.23684859.v5 19 Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain References 1. World Health Organization: Tuberculosis (TB). [Accessed 9 February 2022]. Reference Source 2. TBFacts: TB Statistics, India. [Accessed 9 February 2022]. Reference Source 3. Bhargava A: Social determinants of tuberculosis: context, framework, and the way forward to ending TB in India. Taylor & Francis; [Accessed 26 July 2022]. Publisher Full Text 4. Molicotti P, Bua A, Zanetti S: Cost-effectiveness in the diagnosis of tuberculosis: choices in developing countries. J. Infect. Dev. Ctries. 2014; 8 (01): 024–038. PubMed Abstract | Publisher Full Text 5. Singh P: Diagnosis of TB from conventional to modern molecular protocols. Front. Biosci. 2019; 11 (1): 38–60. PubMed Abstract | Publisher Full Text 6. Yin Y, Kuai S, Liu J, et al. : Pretreatment neutrophil-to-lymphocyte ratio in peripheral blood was associated with pulmonary tuberculosis retreatment. Arch. Med. Sci. 2017; 13 (2): 404–411. PubMed Abstract | Publisher Full Text 7. Han Y, Kim SJ, Lee SH, et al. : High blood neutrophil-lymphocyte ratio associated with poor outcomes in miliary tuberculosis. J. Thorac. Dis. 2018 Jan; 10 (1): 339–346. PubMed Abstract | Publisher Full Text | Free Full Text 8. Miyahara R, Piyaworawong S, Naranbhai V, et al. : Predicting the risk of pulmonary tuberculosis based on the neutrophil-to-lymphocyte ratio at TB screening in HIV-infected individuals. BMC Infect. Dis. 2019; 19 : 667. PubMed Abstract | Publisher Full Text | Free Full Text 9. Iliaz S, Iliaz R, Ortakoylu G, et al. : Value of neutrophil/lymphocyte ratio in the differential diagnosis of sarcoidosis and tuberculosis. Ann. Thorac. Med. 2014 Oct; 9 (4): 232–235. PubMed Abstract | Publisher Full Text | Free Full Text 10. Chen G, Wu C, Luo Z, et al. : Platelet-lymphocyte ratios: a potential marker for pulmonary tuberculosis diagnosis in COPD patients. Int. J. Chron. Obstruct. Pulmon. Dis. 2016 Nov 3; 11 : 2737–2740. PubMed Abstract | Publisher Full Text | Free Full Text 11. Iqbal S, Ahmed U, Khan MA: Haematological parameters altered in tuberculosis. Pak. J. Physiol. 2015 Mar 31; 11 (1): 13–16. 12. Okeke CO, Amilo GI, Ifeanyichukwu MO, et al. : Longitudinal assessment of the impact of tuberculosis infection and treatment on monocyte–lymphocyte ratio, neutrophil-lymphocyte ratio, and other white blood cell parameters. Egypt. J. Haematol. 2020 Apr 1; 45 (2): 97. Publisher Full Text 13. Yoon NB, Son C, Um SJ: Role of the neutrophil-lymphocyte count ratio in the differential diagnosis between pulmonary tuberculosis and bacterial community-acquired pneumonia. Ann. Lab. Med. 2013 Mar 1; 33 (2): 105–110. PubMed Abstract | Publisher Full Text | Free Full Text 14. Jeon Y, Lee WI, Kang SY, et al. : Neutrophil-to-Monocyte-Plus-Lymphocyte Ratio as a Potential Marker for Discriminating Pulmonary Tuberculosis from Nontuberculosis Infectious Lung Diseases. Lab. Med. 2019 Jul 16; 50 (3): 286–291. Publisher Full Text 15. Rees CA, Pineros DB, Amour M, et al. : The potential of CBC-derived ratios (monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte) to predict or diagnose incident TB infection in Tanzanian adolescents. BMC Infect. Dis. 2020; 20 (1): 609. PubMed Abstract | Publisher Full Text | Free Full Text 16. The Lancet Infectious Diseases. Correction to Lancet Infect. Dis. 2020. published online Feb 18. 17. Jarosławski S, Pai M: Why are inaccurate tuberculosis serological tests widely used in the Indian private healthcare sector? A root-cause analysis. J. Epidemiol. Glob. Health. 2012; 2 (1): 39–50. PubMed Abstract | Publisher Full Text | Free Full Text 18. Nayak R, Rai S: Data Excel sheet for Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India. figshare. [Dataset]. 2024. Publisher Full Text 19. Nayak R, Rai S: Statistical analysis for Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India. figshare. [Dataset]. 2024. Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 05 Jul 2024 ADD YOUR COMMENT Comment Author details Author details 1 Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India Poorva Bakshi Roles: Data Curation, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Rakshatha Nayak Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Sharada Rai Roles: Conceptualization, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Shikha Jayasheelan Roles: Conceptualization, Data Curation, Methodology, Supervision, Validation, Visualization, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 08 Jan 2025, 13:747 https://doi.org/10.12688/f1000research.150685.2 version 1 Published: 05 Jul 2024, 13:747 https://doi.org/10.12688/f1000research.150685.1 Copyright © 2025 Bakshi P et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Bakshi P, Nayak R, Rai S and Jayasheelan S. Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.12688/f1000research.150685.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 08 Jan 2025 Revised Views 0 Cite How to cite this report: Kusmiati T. Reviewer Report For: Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.5256/f1000research.176494.r357265 ) The direct URL for this report is: https://f1000research.com/articles/13-747/v2#referee-response-357265 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 31 Jan 2025 Tutik Kusmiati , Universitas Airlangga – Dr. Soetomo General Academic Hospital, Surabaya, Indonesia Approved VIEWS 0 https://doi.org/10.5256/f1000research.176494.r357265 The manuscript has been appropriately ... Continue reading READ ALL The manuscript has been appropriately updated. I have no further comment. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Pulmonology and Respiratory Medicine I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Kusmiati T. Reviewer Report For: Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.5256/f1000research.176494.r357265 ) The direct URL for this report is: https://f1000research.com/articles/13-747/v2#referee-response-357265 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 05 Feb 2025 Rakshatha Nayak , Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 576104, India 05 Feb 2025 Author Response Dear Madam, Thank you for reviewing our article. Competing Interests: None Dear Madam, Thank you for reviewing our article. Dear Madam, Thank you for reviewing our article. Competing Interests: None Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 05 Feb 2025 Rakshatha Nayak , Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 576104, India 05 Feb 2025 Author Response Dear Madam, Thank you for reviewing our article. Competing Interests: None Dear Madam, Thank you for reviewing our article. Dear Madam, Thank you for reviewing our article. Competing Interests: None Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Gatechompol S. Reviewer Report For: Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.5256/f1000research.176494.r357264 ) The direct URL for this report is: https://f1000research.com/articles/13-747/v2#referee-response-357264 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 17 Jan 2025 Sivaporn Gatechompol , HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand Approved VIEWS 0 https://doi.org/10.5256/f1000research.176494.r357264 The manuscript has been appropriately ... Continue reading READ ALL The manuscript has been appropriately updated. I have no further comment. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Infectious disease, focus on TB and HIV I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Gatechompol S. Reviewer Report For: Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.5256/f1000research.176494.r357264 ) The direct URL for this report is: https://f1000research.com/articles/13-747/v2#referee-response-357264 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 24 Jan 2025 Rakshatha Nayak , Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 576104, India 24 Jan 2025 Author Response Dear Madam, Thank you for reviewing our article. Competing Interests: None Dear Madam, Thank you for reviewing our article. Dear Madam, Thank you for reviewing our article. Competing Interests: None Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 24 Jan 2025 Rakshatha Nayak , Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 576104, India 24 Jan 2025 Author Response Dear Madam, Thank you for reviewing our article. Competing Interests: None Dear Madam, Thank you for reviewing our article. Dear Madam, Thank you for reviewing our article. Competing Interests: None Close Report a concern COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 05 Jul 2024 Views 0 Cite How to cite this report: Kusmiati T. Reviewer Report For: Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.5256/f1000research.165277.r336227 ) The direct URL for this report is: https://f1000research.com/articles/13-747/v1#referee-response-336227 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 13 Nov 2024 Tutik Kusmiati , Universitas Airlangga – Dr. Soetomo General Academic Hospital, Surabaya, Indonesia Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.165277.r336227 in abstract: I agree that ZN has low sensitivity, but the culture sensitivity is very good. in introduction: In the introduction: you only wrote the reason for studying MLR because ZN is not sensitive and the ... Continue reading READ ALL in abstract: I agree that ZN has low sensitivity, but the culture sensitivity is very good. in introduction: In the introduction: you only wrote the reason for studying MLR because ZN is not sensitive and the source of funds for molecular examination is expensive. In my opinion, a more appropriate reason is: the difficulty of obtaining sputum samples to evaluate treatment because in more than 2 weeks of treatment the patient's complaints have decreased so that it is difficult to produce sputum because they are no longer coughing in Method: In the control group that was included only fever, why was the cough not asked, why was a chest X-ray not performed to rule out that the patient really did not have TB? As we know, there is clinically confirmed TB, namely if there are complaints that point to TB, the CXR results support TB but the bacteriological results are negative. To minimize bias, do you exclude patients with Diabetes and HIV because they are immunocompromised patients which can affect MMR and NLR values? Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Pulmonology and Respiratory Medicine I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Kusmiati T. Reviewer Report For: Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.5256/f1000research.165277.r336227 ) The direct URL for this report is: https://f1000research.com/articles/13-747/v1#referee-response-336227 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 08 Jan 2025 Rakshatha Nayak , Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 576104, India 08 Jan 2025 Author Response Dear Madam, Thank you for reviewing our article and providing valuable feedback. In response to your suggestions, we have made the following revisions: We have revised the abstract ... Continue reading Dear Madam, Thank you for reviewing our article and providing valuable feedback. In response to your suggestions, we have made the following revisions: We have revised the abstract to mention the other disadvantages of AFB culture, as opposed to focusing solely on its sensitivity, as per your recommendation. We agree with your point that obtaining sputum can be difficult in patients who do not present with a cough. We have added this concern as an additional point in the introduction to highlight the challenges involved. The study involved all patients presenting with fever, including those with extrapulmonary TB. Therefore, while we did inquire about symptoms such as cough and other clinical features, these were not specifically emphasized in the article. Following your suggestion, we have now included this information under the inclusion criteria in the methodology section (Version 2). We selected controls based on clinical, radiological, microbiological, and molecular findings to ensure that only true negative TB cases were included. We did not include TB patients without fever, as the subjects were selected from a fever OPD, which is mentioned in the study's limitations under discussion. Despite this limitation, we believe the study remains highly relevant, given that fever is the most common symptom in both pulmonary and extrapulmonary TB cases. We have excluded patients with known comorbidities as mentioned in Version 1. But as per your suggestion, we have specified few such as diabetes and HIV, as noted in the exclusion criteria section of the article in version 2. The article has been revised in accordance with the suggestions provided by the reviewers. We kindly request you to review the updated version of the article and share your valuable comments and approval. We have put sincere efforts into refining the study to enhance its accuracy and applicability, particularly in remote areas, to help reduce the global burden of tuberculosis. We look forward to your feedback. Dear Madam, Thank you for reviewing our article and providing valuable feedback. In response to your suggestions, we have made the following revisions: We have revised the abstract to mention the other disadvantages of AFB culture, as opposed to focusing solely on its sensitivity, as per your recommendation. We agree with your point that obtaining sputum can be difficult in patients who do not present with a cough. We have added this concern as an additional point in the introduction to highlight the challenges involved. The study involved all patients presenting with fever, including those with extrapulmonary TB. Therefore, while we did inquire about symptoms such as cough and other clinical features, these were not specifically emphasized in the article. Following your suggestion, we have now included this information under the inclusion criteria in the methodology section (Version 2). We selected controls based on clinical, radiological, microbiological, and molecular findings to ensure that only true negative TB cases were included. We did not include TB patients without fever, as the subjects were selected from a fever OPD, which is mentioned in the study's limitations under discussion. Despite this limitation, we believe the study remains highly relevant, given that fever is the most common symptom in both pulmonary and extrapulmonary TB cases. We have excluded patients with known comorbidities as mentioned in Version 1. But as per your suggestion, we have specified few such as diabetes and HIV, as noted in the exclusion criteria section of the article in version 2. The article has been revised in accordance with the suggestions provided by the reviewers. We kindly request you to review the updated version of the article and share your valuable comments and approval. We have put sincere efforts into refining the study to enhance its accuracy and applicability, particularly in remote areas, to help reduce the global burden of tuberculosis. We look forward to your feedback. Competing Interests: There are no competing interests Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 08 Jan 2025 Rakshatha Nayak , Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 576104, India 08 Jan 2025 Author Response Dear Madam, Thank you for reviewing our article and providing valuable feedback. In response to your suggestions, we have made the following revisions: We have revised the abstract ... Continue reading Dear Madam, Thank you for reviewing our article and providing valuable feedback. In response to your suggestions, we have made the following revisions: We have revised the abstract to mention the other disadvantages of AFB culture, as opposed to focusing solely on its sensitivity, as per your recommendation. We agree with your point that obtaining sputum can be difficult in patients who do not present with a cough. We have added this concern as an additional point in the introduction to highlight the challenges involved. The study involved all patients presenting with fever, including those with extrapulmonary TB. Therefore, while we did inquire about symptoms such as cough and other clinical features, these were not specifically emphasized in the article. Following your suggestion, we have now included this information under the inclusion criteria in the methodology section (Version 2). We selected controls based on clinical, radiological, microbiological, and molecular findings to ensure that only true negative TB cases were included. We did not include TB patients without fever, as the subjects were selected from a fever OPD, which is mentioned in the study's limitations under discussion. Despite this limitation, we believe the study remains highly relevant, given that fever is the most common symptom in both pulmonary and extrapulmonary TB cases. We have excluded patients with known comorbidities as mentioned in Version 1. But as per your suggestion, we have specified few such as diabetes and HIV, as noted in the exclusion criteria section of the article in version 2. The article has been revised in accordance with the suggestions provided by the reviewers. We kindly request you to review the updated version of the article and share your valuable comments and approval. We have put sincere efforts into refining the study to enhance its accuracy and applicability, particularly in remote areas, to help reduce the global burden of tuberculosis. We look forward to your feedback. Dear Madam, Thank you for reviewing our article and providing valuable feedback. In response to your suggestions, we have made the following revisions: We have revised the abstract to mention the other disadvantages of AFB culture, as opposed to focusing solely on its sensitivity, as per your recommendation. We agree with your point that obtaining sputum can be difficult in patients who do not present with a cough. We have added this concern as an additional point in the introduction to highlight the challenges involved. The study involved all patients presenting with fever, including those with extrapulmonary TB. Therefore, while we did inquire about symptoms such as cough and other clinical features, these were not specifically emphasized in the article. Following your suggestion, we have now included this information under the inclusion criteria in the methodology section (Version 2). We selected controls based on clinical, radiological, microbiological, and molecular findings to ensure that only true negative TB cases were included. We did not include TB patients without fever, as the subjects were selected from a fever OPD, which is mentioned in the study's limitations under discussion. Despite this limitation, we believe the study remains highly relevant, given that fever is the most common symptom in both pulmonary and extrapulmonary TB cases. We have excluded patients with known comorbidities as mentioned in Version 1. But as per your suggestion, we have specified few such as diabetes and HIV, as noted in the exclusion criteria section of the article in version 2. The article has been revised in accordance with the suggestions provided by the reviewers. We kindly request you to review the updated version of the article and share your valuable comments and approval. We have put sincere efforts into refining the study to enhance its accuracy and applicability, particularly in remote areas, to help reduce the global burden of tuberculosis. We look forward to your feedback. Competing Interests: There are no competing interests Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Gatechompol S. Reviewer Report For: Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.5256/f1000research.165277.r308652 ) The direct URL for this report is: https://f1000research.com/articles/13-747/v1#referee-response-308652 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 21 Aug 2024 Sivaporn Gatechompol , HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.165277.r308652 I am pleased to review this work. This is a case-control study in a tertiary hospital in India. The study aimed to assess the usefulness of Neutrophil to Lymphocyte ratio (NLR) and Monocyte to Lymphocyte ratio (MLR) for diagnosing tuberculosis. ... Continue reading READ ALL I am pleased to review this work. This is a case-control study in a tertiary hospital in India. The study aimed to assess the usefulness of Neutrophil to Lymphocyte ratio (NLR) and Monocyte to Lymphocyte ratio (MLR) for diagnosing tuberculosis. I have some comments as following Methods 1. The TB case definition is not clear. Which type of TB were included in the study (i.e pulmonary, extrapulmonry, or both) ? 2. What is the HIV status of the participants ? Since HIV has direclty effect on both NLR and MLR. 3. The patients who had fever but tested negative for TB by AFB culture, ZN stain, or NAAT were assigned to the control group. How can the authors exclude smear/culture negative TB for this group ? Results 1. The authors mentioned in discussion that NLR and MLR can also vary significantly between individuals based on factors like age, sex, and ethnicity. But the authors did not provide these informations in the results or compare between cases and controls. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Infectious disease, focus on TB and HIV I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Gatechompol S. Reviewer Report For: Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.5256/f1000research.165277.r308652 ) The direct URL for this report is: https://f1000research.com/articles/13-747/v1#referee-response-308652 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 08 Jan 2025 Rakshatha Nayak , Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 576104, India 08 Jan 2025 Author Response Dear Madam, Thank you for reviewing our article and providing us with your valuable insights. In response to your suggestions, we have made the following revisions: The study ... Continue reading Dear Madam, Thank you for reviewing our article and providing us with your valuable insights. In response to your suggestions, we have made the following revisions: The study included all patients with fever, encompassing both pulmonary and extrapulmonary TB cases. This information has been added to the inclusion criteria in the methodology section. We have excluded patients with known comorbidities as mentioned in Version 1. But as per your suggestion, we have specified few such as diabetes and HIV, as noted in the exclusion criteria section of the article in version 2 The controls were classified as true negatives after evaluating all clinical, radiological, microbiological, and molecular findings. This update has been reflected in the methodology section. There was no significant difference between age groups or sexes, and we have updated the results accordingly. Regarding ethnicity, we acknowledge the complexity of making comparisons in India due to the immense diversity across ethnic, linguistic, religious, and cultural lines, as well as historical, social, political, and genetic factors. As such, broad comparisons or generalizations about ethnicity would oversimplify the situation, and we have refrained from including such comparisons in the article. The article has been updated as per the suggestions provided by the reviewers. We kindly request you to review the updated version of the article and share your valuable feedback and approval. We have put sincere efforts into refining the study to enhance its accuracy and applicability, particularly in remote areas, to help reduce the global burden of tuberculosis. We look forward to your feedback. Dear Madam, Thank you for reviewing our article and providing us with your valuable insights. In response to your suggestions, we have made the following revisions: The study included all patients with fever, encompassing both pulmonary and extrapulmonary TB cases. This information has been added to the inclusion criteria in the methodology section. We have excluded patients with known comorbidities as mentioned in Version 1. But as per your suggestion, we have specified few such as diabetes and HIV, as noted in the exclusion criteria section of the article in version 2 The controls were classified as true negatives after evaluating all clinical, radiological, microbiological, and molecular findings. This update has been reflected in the methodology section. There was no significant difference between age groups or sexes, and we have updated the results accordingly. Regarding ethnicity, we acknowledge the complexity of making comparisons in India due to the immense diversity across ethnic, linguistic, religious, and cultural lines, as well as historical, social, political, and genetic factors. As such, broad comparisons or generalizations about ethnicity would oversimplify the situation, and we have refrained from including such comparisons in the article. The article has been updated as per the suggestions provided by the reviewers. We kindly request you to review the updated version of the article and share your valuable feedback and approval. We have put sincere efforts into refining the study to enhance its accuracy and applicability, particularly in remote areas, to help reduce the global burden of tuberculosis. We look forward to your feedback. Competing Interests: There are no competing interests Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 08 Jan 2025 Rakshatha Nayak , Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 576104, India 08 Jan 2025 Author Response Dear Madam, Thank you for reviewing our article and providing us with your valuable insights. In response to your suggestions, we have made the following revisions: The study ... Continue reading Dear Madam, Thank you for reviewing our article and providing us with your valuable insights. In response to your suggestions, we have made the following revisions: The study included all patients with fever, encompassing both pulmonary and extrapulmonary TB cases. This information has been added to the inclusion criteria in the methodology section. We have excluded patients with known comorbidities as mentioned in Version 1. But as per your suggestion, we have specified few such as diabetes and HIV, as noted in the exclusion criteria section of the article in version 2 The controls were classified as true negatives after evaluating all clinical, radiological, microbiological, and molecular findings. This update has been reflected in the methodology section. There was no significant difference between age groups or sexes, and we have updated the results accordingly. Regarding ethnicity, we acknowledge the complexity of making comparisons in India due to the immense diversity across ethnic, linguistic, religious, and cultural lines, as well as historical, social, political, and genetic factors. As such, broad comparisons or generalizations about ethnicity would oversimplify the situation, and we have refrained from including such comparisons in the article. The article has been updated as per the suggestions provided by the reviewers. We kindly request you to review the updated version of the article and share your valuable feedback and approval. We have put sincere efforts into refining the study to enhance its accuracy and applicability, particularly in remote areas, to help reduce the global burden of tuberculosis. We look forward to your feedback. Dear Madam, Thank you for reviewing our article and providing us with your valuable insights. In response to your suggestions, we have made the following revisions: The study included all patients with fever, encompassing both pulmonary and extrapulmonary TB cases. This information has been added to the inclusion criteria in the methodology section. We have excluded patients with known comorbidities as mentioned in Version 1. But as per your suggestion, we have specified few such as diabetes and HIV, as noted in the exclusion criteria section of the article in version 2 The controls were classified as true negatives after evaluating all clinical, radiological, microbiological, and molecular findings. This update has been reflected in the methodology section. There was no significant difference between age groups or sexes, and we have updated the results accordingly. Regarding ethnicity, we acknowledge the complexity of making comparisons in India due to the immense diversity across ethnic, linguistic, religious, and cultural lines, as well as historical, social, political, and genetic factors. As such, broad comparisons or generalizations about ethnicity would oversimplify the situation, and we have refrained from including such comparisons in the article. The article has been updated as per the suggestions provided by the reviewers. We kindly request you to review the updated version of the article and share your valuable feedback and approval. We have put sincere efforts into refining the study to enhance its accuracy and applicability, particularly in remote areas, to help reduce the global burden of tuberculosis. We look forward to your feedback. Competing Interests: There are no competing interests Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 05 Jul 2024 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 2 (revision) 08 Jan 25 read read Version 1 05 Jul 24 read read Sivaporn Gatechompol , HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand Tutik Kusmiati , Universitas Airlangga – Dr. Soetomo General Academic Hospital, Surabaya, Indonesia Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Kusmiati T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 31 Jan 2025 | for Version 2 Tutik Kusmiati , Universitas Airlangga – Dr. Soetomo General Academic Hospital, Surabaya, Indonesia 0 Views copyright © 2025 Kusmiati T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The manuscript has been appropriately updated. I have no further comment. Competing Interests No competing interests were disclosed. Reviewer Expertise Pulmonology and Respiratory Medicine I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (1) Author Response 05 Feb 2025 Rakshatha Nayak, Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 576104, India Dear Madam, Thank you for reviewing our article. View more View less Competing Interests None reply Respond Report a concern Kusmiati T. Peer Review Report For: Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.5256/f1000research.176494.r357265) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-747/v2#referee-response-357265 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Gatechompol S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 17 Jan 2025 | for Version 2 Sivaporn Gatechompol , HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand 0 Views copyright © 2025 Gatechompol S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The manuscript has been appropriately updated. I have no further comment. Competing Interests No competing interests were disclosed. Reviewer Expertise Infectious disease, focus on TB and HIV I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (1) Author Response 24 Jan 2025 Rakshatha Nayak, Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 576104, India Dear Madam, Thank you for reviewing our article. View more View less Competing Interests None reply Respond Report a concern Gatechompol S. Peer Review Report For: Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.5256/f1000research.176494.r357264) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-747/v2#referee-response-357264 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Kusmiati T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 13 Nov 2024 | for Version 1 Tutik Kusmiati , Universitas Airlangga – Dr. Soetomo General Academic Hospital, Surabaya, Indonesia 0 Views copyright © 2024 Kusmiati T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions in abstract: I agree that ZN has low sensitivity, but the culture sensitivity is very good. in introduction: In the introduction: you only wrote the reason for studying MLR because ZN is not sensitive and the source of funds for molecular examination is expensive. In my opinion, a more appropriate reason is: the difficulty of obtaining sputum samples to evaluate treatment because in more than 2 weeks of treatment the patient's complaints have decreased so that it is difficult to produce sputum because they are no longer coughing in Method: In the control group that was included only fever, why was the cough not asked, why was a chest X-ray not performed to rule out that the patient really did not have TB? As we know, there is clinically confirmed TB, namely if there are complaints that point to TB, the CXR results support TB but the bacteriological results are negative. To minimize bias, do you exclude patients with Diabetes and HIV because they are immunocompromised patients which can affect MMR and NLR values? Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Pulmonology and Respiratory Medicine I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 08 Jan 2025 Rakshatha Nayak, Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 576104, India Dear Madam, Thank you for reviewing our article and providing valuable feedback. In response to your suggestions, we have made the following revisions: We have revised the abstract to mention the other disadvantages of AFB culture, as opposed to focusing solely on its sensitivity, as per your recommendation. We agree with your point that obtaining sputum can be difficult in patients who do not present with a cough. We have added this concern as an additional point in the introduction to highlight the challenges involved. The study involved all patients presenting with fever, including those with extrapulmonary TB. Therefore, while we did inquire about symptoms such as cough and other clinical features, these were not specifically emphasized in the article. Following your suggestion, we have now included this information under the inclusion criteria in the methodology section (Version 2). We selected controls based on clinical, radiological, microbiological, and molecular findings to ensure that only true negative TB cases were included. We did not include TB patients without fever, as the subjects were selected from a fever OPD, which is mentioned in the study's limitations under discussion. Despite this limitation, we believe the study remains highly relevant, given that fever is the most common symptom in both pulmonary and extrapulmonary TB cases. We have excluded patients with known comorbidities as mentioned in Version 1. But as per your suggestion, we have specified few such as diabetes and HIV, as noted in the exclusion criteria section of the article in version 2. The article has been revised in accordance with the suggestions provided by the reviewers. We kindly request you to review the updated version of the article and share your valuable comments and approval. We have put sincere efforts into refining the study to enhance its accuracy and applicability, particularly in remote areas, to help reduce the global burden of tuberculosis. We look forward to your feedback. View more View less Competing Interests There are no competing interests reply Respond Report a concern Kusmiati T. Peer Review Report For: Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.5256/f1000research.165277.r336227) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-747/v1#referee-response-336227 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Gatechompol S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 21 Aug 2024 | for Version 1 Sivaporn Gatechompol , HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand 0 Views copyright © 2024 Gatechompol S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I am pleased to review this work. This is a case-control study in a tertiary hospital in India. The study aimed to assess the usefulness of Neutrophil to Lymphocyte ratio (NLR) and Monocyte to Lymphocyte ratio (MLR) for diagnosing tuberculosis. I have some comments as following Methods 1. The TB case definition is not clear. Which type of TB were included in the study (i.e pulmonary, extrapulmonry, or both) ? 2. What is the HIV status of the participants ? Since HIV has direclty effect on both NLR and MLR. 3. The patients who had fever but tested negative for TB by AFB culture, ZN stain, or NAAT were assigned to the control group. How can the authors exclude smear/culture negative TB for this group ? Results 1. The authors mentioned in discussion that NLR and MLR can also vary significantly between individuals based on factors like age, sex, and ethnicity. But the authors did not provide these informations in the results or compare between cases and controls. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Infectious disease, focus on TB and HIV I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (1) Author Response 08 Jan 2025 Rakshatha Nayak, Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 576104, India Dear Madam, Thank you for reviewing our article and providing us with your valuable insights. In response to your suggestions, we have made the following revisions: The study included all patients with fever, encompassing both pulmonary and extrapulmonary TB cases. This information has been added to the inclusion criteria in the methodology section. We have excluded patients with known comorbidities as mentioned in Version 1. But as per your suggestion, we have specified few such as diabetes and HIV, as noted in the exclusion criteria section of the article in version 2 The controls were classified as true negatives after evaluating all clinical, radiological, microbiological, and molecular findings. This update has been reflected in the methodology section. There was no significant difference between age groups or sexes, and we have updated the results accordingly. Regarding ethnicity, we acknowledge the complexity of making comparisons in India due to the immense diversity across ethnic, linguistic, religious, and cultural lines, as well as historical, social, political, and genetic factors. As such, broad comparisons or generalizations about ethnicity would oversimplify the situation, and we have refrained from including such comparisons in the article. The article has been updated as per the suggestions provided by the reviewers. We kindly request you to review the updated version of the article and share your valuable feedback and approval. We have put sincere efforts into refining the study to enhance its accuracy and applicability, particularly in remote areas, to help reduce the global burden of tuberculosis. We look forward to your feedback. View more View less Competing Interests There are no competing interests reply Respond Report a concern Gatechompol S. Peer Review Report For: Deciphering the significance of neutrophil to lymphocyte and monocyte to lymphocyte ratios in tuberculosis: A case-control study from southern India [version 2; peer review: 2 approved] . F1000Research 2025, 13 :747 ( https://doi.org/10.5256/f1000research.165277.r308652) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-747/v1#referee-response-308652 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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