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Serum Zinc Level and Efficacy of Zinc Therapy in Cutaneous Leishmaniasis: a Systematic Review and Meta-analysis

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Abstract

Cutaneous leishmaniasis is a parasitic skin disease prevalent in many parts of the world. Zinc has been investigated for its potential role in the immune response against Leishmania parasites. This study aimed to systematically review the literature and conduct meta-analyses to evaluate the serum zinc level and efficacy of zinc therapy in cutaneous leishmaniasis. A comprehensive search of electronic databases was performed to find studies reporting serum zinc levels and the efficacy of zinc therapy in cutaneous leishmaniasis. Meta-analyses were conducted using RevMan software (version 5.4), calculating the mean difference for serum zinc levels and risk ratio for the efficacy of zinc therapy. A total of 11 studies with 1009 participants were evaluated. Five of these studies, comprising 637 participants, examined serum zinc levels; the remaining six, involving 372 individuals, examined the effectiveness of zinc therapy in treating cutaneous leishmaniasis. The results showed that the serum zinc level was significantly lower in cutaneous leishmaniasis patients compared to controls (MD: − 26.65; 95% CI: [− 42.74, − 10.57]; p = 0.001). However, zinc therapy did not demonstrate a significant clinical improvement compared to standard treatment (RR: 0.96; 95% CI: [0.74, 1.23], p = 0.73).

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References

  1. Sunter J, Gull K (2017) Shape, form, function, and Leishmania pathogenicity: from textbook descriptions to biological understanding. Open Biol 7(9):170165

  2. Barrett AD, Stanberry LR (2009) Vaccines for biodefense and emerging and neglected diseases, 1st edn. Academic Press, London

  3. Leishmaniasis (2023) World Health Organization https://www.who.int/news-room/fact-sheets/detail/leishmaniasis. Accessed 28 April 2023

  4. Moore EM, Lockwood DN (2010) Treatment of visceral leishmaniasis. J Glob Infect Dis 2:151–158. https://doi.org/10.4103/0974-777x.62883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Henao HH, Osorio Y, Saravia NG, Gómez A, Travi B (2004) Efficacy and toxicity of pentavalent antimonials (Glucantime® and Pentostam®) in an American cutaneous leishmaniasis animal model: luminometry application. Biomedica 24:393–402

    Article  PubMed  Google Scholar 

  6. Blum J, Desjeux P, Schwartz E, Beck B, Hatz C (2004) Treatment of cutaneous leishmaniasis among travellers. J Antimicrob Chemother 53:158–166. https://doi.org/10.1093/jac/dkh058

    Article  CAS  PubMed  Google Scholar 

  7. Nweze JA, Nweze EI, Onoja US (2020) Nutrition, malnutrition, and leishmaniasis. Nutrition 73:110712. https://doi.org/10.1016/j.nut.2019.110712

    Article  CAS  PubMed  Google Scholar 

  8. Schroeder HA, Nason AP, Tipton IH, Balassa JJ (1966) Essential trace metals in man: copper. J Chronic Dis 19:1007–1034. https://doi.org/10.1016/0021-9681(66)90033-6

    Article  CAS  PubMed  Google Scholar 

  9. Ursini F, Bindoli A (1987) The role of selenium peroxidases in the protection against oxidative damage of membranes. Chem Phys Lipids 44:255–276. https://doi.org/10.1016/0009-3084(87)90053-3

    Article  CAS  PubMed  Google Scholar 

  10. Tudor R, Zalewski PD, Ratnaike RN (2005) Zinc in health and chronic disease. J Nutr Health Aging 9:45–51

    CAS  PubMed  Google Scholar 

  11. Gammoh NZ, Rink L (2017) Zinc in infection and inflammation. Nutrients 9(6):624

  12. Ahmad A (1997) Visceral leishmaniasis in Southern Ethiopia II. Nutritional risk factors. Ethiop J Health Dev 11(2):139–144

  13. Pourfallah F, Javadian S, Zamani Z, Saghiri R, Sadeghi S, Zarea B et al (2009) Evaluation of serum levels of zinc, copper, iron, and zinc/copper ratio in cutaneous leishmaniasis. Iran J Arthropod-borne Dis 3:7

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Iraji F, Vali A, Asilian A, Shahtalebi MA, Momeni AZ (2004) Comparison of intralesionally injected zinc sulfate with meglumine antimoniate in the treatment of acute cutaneous leishmaniasis. Dermatology 209:46–49. https://doi.org/10.1159/000078586

    Article  CAS  PubMed  Google Scholar 

  15. Maleki M, Karimi G, Tafaghodi M, Raftari S, Nahidi Y (2012) Comparison of intralesional two percent zinc sulfate and Glucantime injection in treatment of acute cutaneous leishmaniasis. Indian J Dermatol 57:118–122. https://doi.org/10.4103/0019-5154.94279

    Article  PubMed  PubMed Central  Google Scholar 

  16. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-p) 2015 statement. Syst Rev 4:1. https://doi.org/10.1186/2046-4053-4-1

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wells G, Shea B, O’Connell D, Peterson J (2000) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 10 Apr 2023

  18. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I et al (2019) Rob 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898. https://doi.org/10.1136/bmj.l4898

    Article  PubMed  Google Scholar 

  19. Revman 5 (review manager [RevMan], [computer program], version 5.4.1, the Cochrane collaboration, 2020)

  20. Sattar F, Akram S, Akhtar A, Almas U, Tahir R, Nawaz S (2020) Efficacy of oral zinc sulphate compared with intralesional meglumine antimoniate injection (Glucantime) in the treatment of cutaneous leishmaniasis. J Pak Assoc Dermatol 30:111–116

    Google Scholar 

  21. Yazdanpanah MJ, Banihashemi M, Pezeshkpoor F, Khajedaluee M, Famili S, Tavakoli Rodi I et al (2011) Comparison of oral zinc sulfate with systemic meglumine antimoniate in the treatment of cutaneous leishmaniasis. Dermatol Res Pract 2011:269515. https://doi.org/10.1155/2011/269515

    Article  PubMed  PubMed Central  Google Scholar 

  22. Farajzadeh S, Ahmadi R, Mohammadi S, Pardakhty A, Khalili M, Aflatoonian M (2018) Evaluation of the efficacy of intralesional Glucantime plus niosomal zinc sulphate in comparison with intralesional Glucantime plus cryotherapy in the treatment of acute cutaneous leishmaniasis, a randomized clinical trial. J Parasit Dis 42:616–620. https://doi.org/10.1007/s12639-018-1044-5

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sharquie K, Noaimi A, Sharara Z, Saleh B, Al-Salam W (2017) Topical therapy of acute cutaneous leishmaniasis using zinc sulphate solution 25% versus podophyllin solution 25%. JCDSA 07:258–274. https://doi.org/10.4236/jcdsa.2017.73024

    Article  CAS  Google Scholar 

  24. Kocyigit A, Gur S, Erel O, Gurel MS (2002) Associations among plasma selenium, zinc, copper, and iron concentrations and immunoregulatory cytokine levels in patients with cutaneous leishmaniasis. Biol Trace Elem Res 90:47–55. https://doi.org/10.1385/BTER:90:1-3:47

    Article  CAS  PubMed  Google Scholar 

  25. Kocyigit A, Erel O, Seyrek A, Gurel MS, Aktepe N, Avci S et al (1998) Effects of antimonial therapy on serum zinc, copper and iron concentrations in patients with cutaneous leishmaniasis in turkey. J Egypt Soc Parasitol 28:133–142

    CAS  PubMed  Google Scholar 

  26. Kahvaz MS, Soltani S, Soltani S, Carvalheiro MC, Foroutan M (2021) Low serum levels of selenium, zinc, iron, and zinc/copper ratio in an endemic region of cutaneous leishmaniasis in southwest Iran. Biol Trace Elem Res 199:1291–1296. https://doi.org/10.1007/s12011-020-02271-z

    Article  CAS  PubMed  Google Scholar 

  27. Farzin L, Moassesi ME (2014) A comparison of serum selenium, zinc and copper level in visceral and cutaneous leishmaniasis. J Res Med Sci 19:355–357

    PubMed  PubMed Central  Google Scholar 

  28. Hegde ML, Shanmugavelu P, Vengamma B, Rao TS, Menon RB, Rao RV et al (2004) Serum trace element levels and the complexity of inter-element relations in patients with Parkinson’s disease. J Trace Elem Med Biol 18:163–171. https://doi.org/10.1016/j.jtemb.2004.09.003

    Article  CAS  PubMed  Google Scholar 

  29. Shahi M, Mohajery M, Shamsian SA, Nahrevanian H, Yazdanpanah SM (2013) Comparison of th1 and th2 responses in non-healing and healing patients with cutaneous leishmaniasis. Rep Biochem Mol Biol 1:43–48

    PubMed  PubMed Central  Google Scholar 

  30. Louzir H, Melby PC, Ben Salah A, Marrakchi H, Aoun K, Ben Ismail R et al (1998) Immunologic determinants of disease evolution in localized cutaneous leishmaniasis due to Leishmania major. J Infect Dis 177:1687–1695. https://doi.org/10.1086/515297

    Article  CAS  PubMed  Google Scholar 

  31. Lee SR (2018) Critical role of zinc as either an antioxidant or a prooxidant in cellular systems. Oxid Med Cell Longev 2018:9156285. https://doi.org/10.1155/2018/9156285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Prasad AS, Bao B (2019) Molecular mechanisms of zinc as a pro-antioxidant mediator: clinical therapeutic implications. Antioxidants 8:164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Klasing KC (1988) Nutritional aspects of leukocytic cytokines. J Nutr 118:1436–1446. https://doi.org/10.1093/jn/118.12.1436

    Article  CAS  PubMed  Google Scholar 

  34. AL-Tikrity GAA (2020) Estimation of interferon gamma and zinc concentration in serum of cutaneous leishmaniasis patients in Tikrit city. Indian J Public Health Res Dev 11:1920–1925

    Article  Google Scholar 

  35. Faryadi M, Mohebali M (2003) Alterations of serum zinc, copper and iron concentrations in patients with acute and chronic cutaneous leishmaniasis. Iran J Public Health 32(4):53–58

  36. Nahidi Y, Mashayekhi Goyonlo V, Layegh P, Marhamati H, Najaf Najafi M (2021) Comparison of serum zinc level in acute improved and chronic cutaneous leishmaniasis. Iran J Dermatol 24:40–45. https://doi.org/10.22034/ijd.2021.128949

    Article  Google Scholar 

  37. Mishra J, Carpenter S, Singh S (2010) Low serum zinc levels in an endemic area of visceral leishmaniasis in Bihar, India. Indian J Med Res 131:793–798

    CAS  PubMed  Google Scholar 

  38. Lal CS, Kumar S, Ranjan A, Rabidas VN, Verma N, Pandey K et al (2013) Comparative analysis of serum zinc, copper, magnesium, calcium and iron level in acute and chronic patients of visceral leishmaniasis. J Trace Elem Med Biol 27:98–102. https://doi.org/10.1016/j.jtemb.2012.09.007

    Article  CAS  PubMed  Google Scholar 

  39. Van Weyenbergh J, Santana G, D’Oliveira A Jr, Santos AF Jr, Costa CH, Carvalho EM et al (2004) Zinc/copper imbalance reflects immune dysfunction in human leishmaniasis: an ex vivo and in vitro study. BMC Infect Dis 4:50. https://doi.org/10.1186/1471-2334-4-50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Maxfield L, Shukla S, Crane JS (2023) Zinc deficiency. Statpearls. Treasure Island (FL): Copyright © 2023, StatPearls Publishing LLC

  41. Carbone DCB, Zanoni LZG, Consolo FZ, Sanches SC, Reis VQD, Muller KTC et al (2018) Potential role of zinc in the visceromegaly regression and recovery of hematological parameters during treatment of visceral leishmaniasis in children from an endemic area. Rev Inst Med Trop Sao Paulo 60:e50. https://doi.org/10.1590/s1678-9946201860050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Jen M, Shah KN, Yan AC (2007) Skin in nutritional, metabolic and heritable disease. In Dermatology in general medicine. Wolff K, Goldsmith LA, and Katz SI (eds). p. 1215, McGraw–Hill, New York, 7th edition, J Dermatol 6:20–24

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Lovely Professional University, Punjab, 144411, India

    Biplab Pal, Ashish Kumar Mishra, Harsh Raj, Vaibhav Chaudhary, Navneet Khurana & Sweta Kumari

  2. Division of Pharmacology, Department of Pharmaceutical Medicine, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India

    Mohammad Azharuddin

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Contributions

BP, AKM, and HR wrote the manuscript. VC, SK, NK, and MA contributed to data collection, analysis, and interpretation. Study concept was conceived by BP and NK. All authors have read and approved the final manuscript.

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Correspondence to Sweta Kumari.

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Pal, B., Mishra, A.K., Raj, H. et al. Serum Zinc Level and Efficacy of Zinc Therapy in Cutaneous Leishmaniasis: a Systematic Review and Meta-analysis. Biol Trace Elem Res 202, 1856–1865 (2024). https://doi.org/10.1007/s12011-023-03797-8

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