JOURNAL CLUB PRESENTATION - CPLE VS PLACEBO IN THE TRETMENT OF DENGUE

Journal Club Presentation on Topic Safety and Efficacy of CPLE vs Placebo in the patients of positive NS1 Antigen Positive Dengue Patients

1. JOURNAL CLUB PRESENTATION Dr. J. B. Jaju Sir Professor and H.O.D. (PG Guide ) Department of Pharmacology SRTRGMC Ambajogai Dr Jyothish Gopinathan N K 1 ST Year Junior Resident Department of Pharmacology SRTRGMC Ambajogai 1 20-02-2024

2. EVALUATION OF THE EFFICACY OF CARICA PAPAYA LEAF EXTRACT ON PLATELET COUNTS IN DENGUE PATIENTS Sulabhsinh G. Solanki*, Priya Trivedi B.N. Patel Institute of Paramedical and Science (Paramedical Division), Anand, Affiliated to Sardar Patel University, Vallabh Vidyanagar, Gujarat, India *Corresponding author: [email protected] Journal of Advanced Scientific Research Year-2020, Volume-8, Page Number-62-65 2 20-02-2024

3. BACKGROUND Dengue is an acute viral infection associated with thrombocytopenia, which is of great public health concern in india. 1 It is the most common arthropod borne viral infection transmitted by mosquitoes by the species of aedes 2 In India a. Aegypti is the main vector in most urban areas and caused by DEN-1,DEN-2,DEN-3 AND DEN-4 types of flavivirus. 3 The clinical manifestation of dengue includes high grade fever, headache, arthralgia, retro orbital pain, back pain, myalgia, and flu like symptoms 4 3 20-02-2024

4. Carica papaya leaves are being used in ayurvedic medicine since many years and i ts use as an anti-inflammatory agent, its wound-healing properties being studied 7 Safety studies for chronic, sub-acute, and acute toxicities were conducted on CPLE and demonstrated to be safe for human consumption based on the OECD guidelines 8 Some of the genes have shown to influence platelet production, namely, arachidonate 12-lipoxygenase (ALOX 12) and platelet-activating factor receptor (PTAFR) 9 4 20-02-2024

5. The ALOX 12 gene is intensely expressed in megakaryocytes, and it has shown to be accountable for the 12 hydroxy eicosatetraenoic acid (12-HETE) production of platelets in patients treated with CPLE 10 Clinical evidence s shows that C. papaya extract enhances the PTAFR activity around 13-fold and the ALOX 12 activity 15-fold 12 which is responsible for increased platelet production 13 5 20-02-2024

6. OBJECTIVE EVALUATION OF THE EFFICACY OF CARICA PAPAYA LEAF EXTRACT ON PLATELET COUNTS IN DENGUE PATIENTS 6 20-02-2024

7. MATERIALS AND METHODS Study Design : Randomised Control Trial Study Sample : 150 Dengue Patients with Thrombocytopenia Study Group : 100 Dengue patients were taken as Study group and 50 dengue patients were taken as Control group 7 20-02-2024

8. INTERVENTION : 5 ml venous blood was collected in a plain bulb (3 ml) and EDTA bulb (2 ml). Then Plain bulb was centrifuged at 2200 RPM for 10 minutes to separate serum. The serum sample was used to perform diagnostic tests for the detection of of NS1 antigen and differential detection of IgM & IgG antibodies in patient’s serum was carried out by using SD Dengue Duo kit method [14]. EDTA bulb was used for the determination of complete blood count, (the hemoglobin, platelet count, white blood cell count, and packed cell volume) was performed. Study group patients of dengue fever with thrombocytopenia (<1,50,000 cells/ cu mm) were given with Carica papaya leaf extract i.e., 10 ml /3 times per day for adults and children 5 ml /3 times per day for 3 days along with one kiwi fruit. 8 20-02-2024

9. COMPARISION : All the subjects were followed up daily for 3 days with monitoring Platelet and WBC count and result was compared with previous one . STATISTICAL ANALYSIS : Paired t-test in SPSS was used to compare the mean values of the parameters in the study group before and after giving CPLE [15]. The p-value <0.05 was considered as statistically highly significant 9 20-02-2024

10. RESULTS All patients recruited were Dengue NS1(AG) / IgM(ab) or both Positive Among 100 patients of study group 58 % were males and 42% were female patients. 10 20-02-2024

11. The platelet count was significantly increased after 3 days [p-value 0.00 (<0.05)] of giving CPLE in the study group. Symptoms of dengue i.e. high fever, vomiting, rashes etc. were also reduced 11 20-02-2024

12. The WBC count was also significantly increased after 3 days (p-value=0.00 (<0.05)) after giving CPLE and reduction in dengue symptoms, i.e. high fever was also observed in study group in comparison with control group Increase in the mean platelet count was considered as the primary outcome, and increase in mean WBC counts was considered as the secondary outcome. 12 20-02-2024

13. DISCUSSION CPLE had significant increases in the platelet count as compared to control group S ignificant increase in the WBC counts in the study group as compared to the control group. Results of the study are corroborative to the previous studies conducted 13,16,17,18&19 The leaf extract of C. papaya has antioxidant and free radical scavenging property which can help in the prevention of hemolysis and bleeding 23-26 . This is so far best available evidence for the use of C. papaya in dengue patients 13 20-02-2024

14. CONCLUSION C arica papaya leaf extract has a definitive role in improving the platelet count and also shows reduction in symptoms as compared to control group The WBC count was also increased significantly in dengue patients with thrombocytopenia as compared to control group Carica papaya leaf extract was well tolerated among the patients as it has not shown any side effects therefore it provides strongest recommendation that it can be added as therapeutic agent in the management of dengue fever as supportive therapy along with allopathic therapy A dd it as supportive therapy for better outcome of the patients. 14 20-02-2024

15. REFERENCES 1. Srikanth B, Reddy L, Biradar S, Shamanna M, Mariguddi D, Krishnakumar M. Pediatric health, medicine and therapeutics , 2019; 10 :5. 2. Venugopal K, Suresh R, Halesha B. International Journal of Advanes in Medicine, 2018; 4(5):845-848. 3. Malange G, Fernando S, and Sinivirante S. Postgrad Med, 2004; 80 :588-601. 4. John K, Gunasekaran K, Prasad J, Mathew D, Das S, Sultan N, Abraham A, Iyyadurai R. Interdisciplinary Perspectives on Infectious Diseases, 2019; 6 :1-7. 5. Malavige M, Neelika G, Graham S. Immunology , 2017; 3(151): 261-269. 6. Kasture S, Nagnathappa P, Nagabhushan K, Kumar A. J Assoc Physicians India, 2016; 6(64): 15-20. 15 20-02-2024

16. 7. Halim S, Abdullah N, Afzan A, Rashid B, Jantan I, Ismail Z. Journal of Medicinal Plants Research, 2011; 5(10): 1867-1872. 8. Manjunath, VG, Sruthi Balla, Jagadish Kumar K. International Journal of Contemporary Pediatrics , 2019; 6(3): 1. 9. Jaykaran C, Saxena D, Goyal J, Yasobant S. International Journal of Applied and Basic Medical Research , 2016; 4(6): 249. 10. Kakhangchung P, Joseph A, Rose W, Abraham O, Mathuram A, Kumar S, Abraham A. International Journal of Infectious Diseases, 2019; 84: S64-S67. 11. Shamsuzzaman A. Journal of Current and Advance Medical Research, 2019; 6(2): 67-68. 12. World Health Organization, 2011. 13. Gowda A, Kumar N, Kasture P, Nagabhushan K. Indian Med Gaz, 2015; 149: 109-116. 14. Vickers I, Harvey K, Brown M, Nelson K, DuCasse M, Lindo J. Journal of Biomedical Science , 2015; 22 (55): 1-7. 16 20-02-2024

17. 15. SPSS statistics for windows, trial version 15.0 (SPSS Inc., Chicago, III., USA). 16. Subenthiran S, Choon T, Cheong K, Thayan R, Teck M, Muniandy P, Afzan A, Abdullah N, Ismail Z. Evidence-Based Complementary and Alternative Medicine, 2013; 1 :1. 17. Venugopal K et al. Int J Adv Med , 2018; 5(4): 845-848. 18. Fenny Y, Hanani E, and Kristianto J. Int J Med Aromat Plants, 2012; 2(4): 573-578. 19. Gupta A, Tyagi V, Malik S, Virmani S, and Singhal S. Journal of Advance Researches in Biological Sciences, 2015; 7(1): 1-4. 20. Iain M, Tijssen M, Thijssen-Timmer D, Gusnanto A, Steward M, Burns P, Langford C et al. Blood , 2007; 8 (109): 3260-3269. 21. Siddique O. J Pak Med Assoc, 2014; 64 :3. 17 20-02-2024

18. 22. Ranasinghe P, Kaushalya W, Abeysekera M, Premakumara G, Perera Y, Gurugama P, Gunatilake S. Pharmacognosy Research, 2012; 4(4): 196. 23. Chakravarti A, Kumar A, Malik S. Southeast Asian Journal of Tropical Medicineand Public Health, 2011; 2 (42): 297. 24. Gadhwal A, Kumar A, Ankit B, Chahar C, Tantia P, Sirohi P, Agrawal R. J Assoc Physicians India, 2016; 6(64): 22-26. 25. Marco M, Martins S, Hugo C, Neto C, Bozza P, Dias P, Cordeiro R, Vargaftig B. European journal of pharmacology, 1988; 1-2(149): 89-96. 26. Tau-Hong L, Wong J, Leo Y, Thein T, Ling N, Lee L, Lye D. PLoS Neglected Tropical Diseases, 2016; 10 (3): e0004576 18 20-02-2024

19. CRITICAL APPRAISAL OF JOURNAL Date of Publication of Article : 2020 , Date and month not mentioned Date of Acceptance :?? Volume : 8 DOI(Digital Object Identifier) : ?? Open Access Journal 19 20-02-2024

20. Financial Support : ?? Conflicts of Interests: ?? Disclaimer : ?? Informed written consent: ?? Ethical Approval: ?? Key Words : Dengue, Thrombocytopenia, CPLE, Platelet count 20 20-02-2024

21. CRITICAL APPRAISAL OF TITLE The title indicates the topic and focus of the study This title is neither long nor short and it does look catchy The research question focussed in terms of PICO tool 21 20-02-2024

22. CRITICAL APPRAISAL OF AUTHOR’S The names of the authors are mentioned clearly The details of author’s institution are mentioned clearly Author’s credential details are not mentioned properly 22 20-02-2024

23. CRITICAL APPRAISAL OF ABSTRACT The abstract of the article is not structured It is of less than 250 words The abstract is informative and meaningful It is comprehensive in content It clearly gives the essence of whole study The abstract could have been be presented in structured format for the easy understanding 23 20-02-2024

24. CRITICAL APPRAISAL OF INTRODUCTION The introduction is meaningful The introduction is logically presented with giving introduction to dengue followed by details of carica papaya leaf extract and finally the importance of the study All the citations are followed with correct references in the list of references Research question was stated in the introduction Significance of Kiwi fruit is not mentioned 24 20-02-2024

25. CRITICAL APPRAISAL OF MATERIALS AND METHODS The study design of the research is appropriate as per the research problem The sample is representative of the population of interest The methods used are appropriate The Study Site is not mentioned in the article Method of randomisation of the groups also been not mentioned 25 20-02-2024

26. Treatment given to the control group not mentioned Inclusion and exclusion criteria of the study subjects also been not mentioned in the article Whether study was conducted after taking informed consent of the study subjects or not also not mentioned Whether the study was conducted after taking the approval of Ethics Committee or not also not mentioned in the Study Time period of the study also not mentioned Because the study subjects also given with the Kiwi fruit, platelet increasing action can't be said to be only resulted due to CPLE , it may be due to Kiwi fruit also; clarity is required in that perspective… 26 20-02-2024

27. CRITICAL APPRAISAL OF RESULTS The results is presented in logical and comprehensible manner All the data are performed in a tabular form and are titled properly All tables are explained All the tables are simple and alignment of information are properly done Statistical numerical are mentioned clearly wherever required 27 20-02-2024

28. CRITICAL APPRAISAL OF DISCUSSION The discussion of the article is meaningful and has highlighted the important findings of the study Results are compared with the previous studies and proper citations are given wherever necessary All the significant findings have enough explanation In this part also they not discussed about significance and differential action between the CPLE and Kiwi fruit 28 20-02-2024

29. CRITICAL APPRAISAL OF CONCLUSION The conclusion is meaningful The conclusion is supported by the results drawn The research question has been answered 29 20-02-2024

30. CRITICAL APPRAISAL OF THE REFERENCES Study is provided with 26 references which is adequate for the study Mentioned all cited References It shows that study has conducted a thorough and appropriate literature search and reading Vancouver System is not used for Bibliography 30 20-02-2024

31. STRENGTHS Article is reliable and useful source for academic and non academic purposes Study able to draw a conclusive answer for the research question 31 20-02-2024

32. WEAKNESS It is has been not mentioned about the criteria of randomisation of the study subjects Inclusion and Exclusion criteria of the study subjects also not mentioned Importance of using Kiwi fruit in the subjects not mentioned in study 32 20-02-2024

33. THANKYOU… 33 20-02-2024