Introduction and objectives: Zoonotic cutaneous leishmaniasis (ZCL) remains a significant health problem, particularly in Iran, where 15.8 cases per 100,000 people were reported in 2019. Iran accounted for more than half of all new cases in the Eastern Mediterranean region in 2008. entified several countries in the Middle East and North Africa, including Syria, Afghanistan, Iran, Pakistan, Iraq, Yemen, Tunisia, Morocco, Libya and Egypt, as having the highest rates of this disease, which is a major burden in the rural areas of these regions. ZCL is a major global health problem, especially in countries such as Iran, the Middle East and North Africa.ZCL is a major global health problem, particularly in countries such as Iran, the Middle East and North Africa. Despite the existing research on cutaneous leishmaniasis, few studies focus exclusively on the epidemiologic aspects of ZCL. This systematic study aims to fill this gap by investigating the geographical distribution and cause of occurrence and identifying reservoirs, vectors and sites of ZCL occurrence, focusing on high-risk areas such as Algeria and Tunisia in North Africa in figure 8. Areas suitable for vector-borne transmission and ZCL reservoirs are expected to increase in the future. Understanding the ecological links between vectors, reservoirs and the Leishmania parasite is crucial for the development of effective control and prevention strategies. It is expected that the regions favorable for vector-borne transmission and the reservoirs of zoonotic cutaneous leishmaniasis (ZCL) will expand as environmental conditions evolve. To develop effective control and prevention strategies, it is important to understand the ecological interplay between vectors, reservoirs and the leishmaniasis parasite. Climate change is expected to exacerbate the threat of ZCL by 2050, potentially increasing the suitability of habitats for vectors and reservoirs. This study uniquely examines the epidemiologic aspects of ZCL globally, filling a gap in the current literature that predominantly addresses cutaneous leishmaniasis in a broader context. Results: This study provides a detailed insight into the increasing prevalence of zoonotic cutaneous leishmaniasis (ZCL) in Iran. It identifies Iran, where 18 out of 31 provinces are affected, as a critical area, especially the central provinces. Key factors such as Leishmania reservoirs in rodents, emerging reservoirs, and specific vectors contribute significantly to the transmission of the disease and are influenced by environmental and climatic conditions in Iran, the Middle East, and North Africa. The study highlights new hotspots in Iran, such as Beyza district in Fars province and regions in Isfahan and Razavi Khorasan provinces, which indicate the dynamic nature of the spread of ZCL associated with urbanization and climate change. Predictive modeling suggests that an increase in ZCL may soon occur in northwestern Iran due to suitable environmental conditions for the vectors and reservoirs. On the other hand, the identification of new reservoirs was an important result. These included different hedgehog species (Paraechinus aethiopicus, Atelerix algirus, and Hemiechinus auritus) in Algeria, Tunisia, and Iran as well as calomyscid rodents in Shiraz, the capital of the Iranian province of Fars. Interestingly, specific vectors and reservoirs make Tunisia and Algeria high-risk areas in North Africa, emphasizing the need for regional integrated control measures. The results highlight a crucial gap in the research and control of zoonotic cutaneous leishmaniasis outside Iran. In the last ten years, the focus has been less on the Middle East and Central Asia, although the disease is widespread in these regions. Conclusion: This review emphasizes the critical need for a combined approach to the control and prevention of zoonotic cutaneous leishmaniasis (ZCL). This study emphasizes the role of climate change and urban expansion in influencing disease dynamics. The identification of new endemic areas and prediction of future hotspots in Iran will provide valuable insights for targeting prevention and control measures. This underlines the importance of regional collaboration and adaptive strategies in the Middle East and North Africa (MENA) countries to effectively tackle this neglected tropical disease as part of the One Health approach. As the first comprehensive study on the epidemiology of ZCL, this study fills a significant gap in the literature and provides a foundation for future research and public health interventions to mitigate the global impact of ZCL. This systematic review highlights the complicated and multifaceted nature of the disease, which is influenced by various vectors, reservoir hosts, and environmental factors. This comprehensive review not only deepens our understanding of the epidemiology of ZCL, but also provides crucial insights for health managers and policy makers. This knowledge can help them to identify high-risk areas, implement targeted prevention measures, and develop effective control programs to combat this endemic disease. Keywords: Zoonotic cutaneous leishmaniasis, Iran, MiddleEast, Epidemiology, Reservoir, Vector, Systematic Review
