Hematological Abnormalities as Diagnostic Indicators of Malaria in Returning Travelers: A Retrospective Study at Mohamed V Military Instruction Hospital

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Abstract

Introduction Malaria remains a significant global health concern, particularly in travelers returning from endemic regions. Hematological abnormalities are often associated with malaria and can serve as diagnostic indicators, especially when clinical symptoms are nonspecific. Objective This study aims to identify the most relevant hematological parameters for diagnosing malaria in travelers returning from endemic areas, who sought care at the Mohamed V Military Instruction Hospital in Rabat. Methods We conducted a retrospective comparative study involving 829 patients who returned from malaria-endemic regions between January 2017 and December 2023. Data collected included demographic information, parasitological test results, and comprehensive hematological profiles. Statistical analysis was performed to determine the sensitivity and specificity of various hematological parameters in diagnosing malaria. Results Thrombocytopenia, lymphocytopenia, and anemia were the most significant hematological abnormalities associated with malaria. Thrombocytopenia, defined as a platelet count below 150 x 103/µL, demonstrated a sensitivity of 75.91% and a specificity of 84.11%. Lymphocytopenia, with a threshold of less than 1.5 x 103/µL, showed a sensitivity of 69.47% and a specificity of 78.39%. Anemia, defined by hemoglobin levels below 13 g/dL in men and 12 g/dL in women, also significantly correlated with malaria diagnosis. Discussion This study highlights the significance of hematological abnormalities as key diagnostic markers for imported malaria cases. By analyzing retrospective data, we observed that these abnormalities, especially thrombocytopenia and anemia, are common among returning travelers with confirmed malaria. These findings suggest that clinicians can use such markers as a valuable tool for early malaria diagnosis, potentially improving patient outcomes. Additionally, the study reinforces the need for heightened awareness among healthcare providers in non-endemic regions regarding the presentation of malaria in travelers. Conclusion Hematological parameters such as thrombocytopenia, lymphocytopenia, and anemia are valuable diagnostic tools for malaria in returning travelers. These findings suggest that these parameters should be integrated into diagnostic protocols to improve the accuracy and timeliness of malaria diagnosis, particularly in clinical settings with limited access to advanced diagnostic tools.

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  1. Dear Dr. Zniber, Your manuscript has been assessed by two independent reviewers, both of which provided positive feedbacks. Yet, a few minor corrections will be necessary. Most importantly, you should provide a better description of the cohort of patients involved in the study, including gender distribution, parasite species, stage of the disease, etc. Moreover, you should acknowledge potential limitations of your study, particuarly regarding the representativeness of its population sample - as the study was performed in a military hospital, please discuss the pontential applicability of these findings for the general population. You will be able to submit your revised manuscript for further consideration once you address the points raised by the reviewers. Please provide a point-by-point response to the reviewers' comments and provide a tracked version of your manuscript when doing so. Best regards, Gustavo

  2. Comments to Author

    Dear Authors I am writing to provide a detailed review of the manuscript "Hematological Abnormalities as Diagnostic Indicators of Malaria in Returning Travelers: A Retrospective Study at Mohamed V Military Instruction Hospital." Below are my comments and suggestions organized according to the criteria provided. 1. Methodological Rigour, Reproducibility, and Availability of Underlying Data - Methodological Rigour: The study's retrospective cohort design and focus on hematological abnormalities as diagnostic markers for malaria are valuable. However, clarity on the inclusion and exclusion criteria would strengthen the study's rigor. Specifically, it is essential to explain how cases with potential confounding conditions (e.g., other infections, hematological disorders) were handled, as this could impact the interpretation of hematological markers. - Reproducibility: The statistical approach, including the choice of logistic regression, is sound. To further enhance reproducibility, a clearer rationale for selecting specific hematological markers in the regression model would be beneficial. Additionally, detailing the thresholds used for classification (e.g., anemia, thrombocytopenia) and providing justification for these cut-offs would improve clarity and reproducibility. - Availability of Data: Although a Jamovi file is mentioned, providing access to anonymized raw data or a summary dataset, where ethical guidelines permit, would facilitate independent verification. For readers with limited statistical software familiarity, consider including code or output settings used in Jamovi, as this could further enhance reproducibility. 2. Presentation of Results - Organization and Clarity: The results section is thorough but would benefit from more streamlined tables. For instance, Tables 1 and 2 could be focused on statistically significant results to draw clearer attention to key findings. Additionally, presenting demographic data in a dedicated table would make it easier for readers to contextualize the study population. - Interpretation of Key Findings**: Consider simplifying some statistical terms or explaining them in non-technical language, particularly when discussing the sensitivity, specificity, and predictive values of thrombocytopenia, lymphocytopenia, and anemia. This would make the diagnostic value of these markers more accessible to a broader audience. - Visual Enhancements: Including a flowchart to illustrate the study process—from patient selection through data analysis—would greatly enhance readability and help convey the research design visually. This would be especially useful for readers less familiar with retrospective study designs. 3. Style and Organization for Communication of Key Findings - Overall Style: The manuscript is well-organized, with clear sections that guide the reader through the study's background, methods, and findings. However, minor adjustments in language would improve readability. For example, the results interpretation could be refined to make key takeaways (such as the predictive power of thrombocytopenia) stand out. - Abstract and Conclusion: The abstract provides a concise overview, but a clearer emphasis on key findings (e.g., sensitivity/specificity values) would strengthen it. Similarly, the conclusion effectively summarizes the study's significance but could further highlight how these findings could potentially impact diagnostic practices, especially in non-endemic regions with limited resources. - Technical Consistency: Ensure consistency in terminology throughout the paper, especially in defining hematological thresholds. This standardization will prevent reader confusion and make the manuscript easier to follow. 4. Literature Analysis or Discussion - Comparison with Existing Literature: The discussion effectively situates the study within the context of existing research, drawing comparisons with similar findings. However, further elaboration on contradictory findings, particularly regarding leukocyte variations across studies, would provide a more balanced perspective. - Clinical Implications: The discussion on the clinical implications of using hematological markers for malaria diagnosis is insightful. Consider expanding on the potential utility of these findings in resource-limited settings, where early diagnosis using basic hematological markers could play a critical role. - Suggestions for Future Research: While the study's limitations are acknowledged, suggesting specific directions for future research, such as prospective studies or multi-site validations, would enhance the manuscript's contribution to the field. 5. Other Relevant Comments - Grammar and Formatting: Minor grammatical inconsistencies should be addressed for improved readability. For instance, in the abstract, correct "Lmyphocytopenia" to "Lymphocytopenia." - Minor Clarifications: Further explanation on the potential effects of the military sample composition on the generalizability of the findings is recommended. As this sample may not represent a typical traveler population, clarifying this limitation could help readers interpret the study's broader applicability. Summary This manuscript provides a valuable analysis of hematological abnormalities in malaria diagnostics and holds potential for enhancing diagnostic accuracy in clinical settings. With some clarifications on methodology, data presentation, and further emphasis on the clinical relevance of findings, this study could significantly contribute to malaria diagnostic research. Thank you for the opportunity to review this insightful manuscript. Please let me know if further clarification on any of the points is needed. Best regards,

    Please rate the manuscript for methodological rigour

    Very good

    Please rate the quality of the presentation and structure of the manuscript

    Very good

    To what extent are the conclusions supported by the data?

    Strongly support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes

  3. Comments to Author

    Thank you for submitting your manuscript. The manuscript by Zniber et al. is highly relevant for the early diagnosis of malaria, particularly in travelers who have returned from endemic areas. The study uses hematological tests routinely used in several clinical analysis laboratories, which makes them easily accessible in many places. However, some issues need to be clarified to validate the tests and improve sensitivity and specificity. The introduction should provide further clarification on the choice of hematological parameters used and their correlation with the pathophysiology and progression of the disease. Are these changes similar for the five species of Plasmodium that infect humans? Each species characterizes different severity and symptomatology. Since this is a retrospective study, I believe there are some limitations regarding the cohort data. However, it would be important to include comorbidities, symptomatology, time of return from endemic areas, days since symptom onset, ethnicity, and concomitant infections. This data would help answer the previous question and standardize the cohort, reducing any bias, in addition to demonstrating whether this study represents the general population or is specific to a group in a given region. Is it possible for the study to establish the range for the reference limits of hematological parameters? The reference standards for validating anemia, leukopenia, leukocytosis, lymphopenia, among others, may vary between different laboratories and therefore may affect the comparison of analyses. Can these parameters be applied to different stages of the disease, from asymptomatic to severe? Would the hematological parameters be the same? Is there any data to support this statement?

    Please rate the manuscript for methodological rigour

    Satisfactory

    Please rate the quality of the presentation and structure of the manuscript

    Satisfactory

    To what extent are the conclusions supported by the data?

    Strongly support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes