J Arthropod-Borne Dis, June 2021, 15(2): 143–151 MR Razavi et al.: Human Cutaneous … 143 http://jad.tums.ac.ir Published Online: June 30, 2021 Review Article Human Cutaneous Leishmaniosis in Iran, Up to Date-2019 Mohamad Reza Razavi1; *Mohammad Reza Shirzadi2,3; Mehdi Mohebali4,5; Mohammad Reza Yaghoobi-Ershadi6; Hassan Vatandoost6; Mehrshad Shirzadi7; Mohammad Mehdi Gouya3; Faranak Gharachorloo3; Shahnam Arshi3; Behzad Amiri3 1Department of Parasitology, Pasteur Institute, Tehran, Iran 2Reserch Center for Zoonoses, Ardabil University of Medical Sciences, Ardabil, Iran 3Center for Communicable Diseases Management, Ministry of Health and Medical Education, Tehran, Iran 4Center for Research Endemic Parasites of Iran, Tehran University of Medical Sciences, Tehran, Iran 5Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 6Department of Medical Entomology and Vector Control, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 7Student of Law, Islamic Azad University, East Branch, Tehran, Iran *Corresponding author: Dr Mohammad Reza Shirzadi; Email: shirzadim@gmail.com (Received 18 Apr 2021; accepted 31 May 2021) Abstract Cutaneous leishmaniasis is a neglected and parasitic vector borne diseases that is endemic in tropical and subtropical countries, including Iran. The aim of this study was to explain the present status of CL in Iran. This report is based on data that recorded by cutaneous leishmaniasis surveillance system in 2019, and evaluated in Center for Communicable Diseases Management in Ministry of Health in Iran. Iran has been considered an endemic area for cutaneous leishmani- asis in the world. Dependent to activities for cutaneous leishmaniasis control the number of cases decreased from 23202 in 2008 (Incidence rate 32 per 100000) to 13124 in 2019 (Incidence rate 15.8 per 100000), more cases reported from September to December, in 2019, 46% of cases had one lesion and 21% had 2 lesions, 85% of cases diagnosed when the diameter of lesions had 3 centimeters and bellows. Although the Leishmania control program began in 1977, the incidence of the disease has dropped dramatically since 2008 when the new cutaneous leishmaniasis control program have been implemented. Although in some areas the inci- dence of the disease increased, but the implementation of the new program has reduced the number of cases, in order to continue reducing the disease, permanent support for the control programs is needed. Keywords: Human cutaneous leishmaniasis; Surveillance; Iran Introduction Leishmaniasis are worldwide parasitic in- fectious diseases caused by protozoa of Leish- mania genus which among them, approximately 20 species are pathogenic for humans (1-2). Natural transmission to mammalian hosts is usually by the bite of female Phlebotomus or Lutzomya sandflies depending on geogra- phy (1). There are three main clinical mani- festations with different degrees of severity on the species of parasite involved and elicited host immune responses. These features including cu- taneous, mucocutaneous and visceral (1, 3-4). Currently, World Health Organization (WHO) lists leishmaniasis amongst the nine most im- portant tropical and subtropical diseases which has been reported in all continents except Oce- ania (1, 3). In 2018, 92 countries or territories were considered endemic for, or had previ- ously reported cases of CL. Today more than 1 billion people live in areas endemic for leishmaniasis and are at risk of infection. Cu- taneous leishmaniasis (CL) is the most com- Copyright © 2021 The Authors. Published by Tehran University of Medical Sciences. This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International license (https://creativecommons.org/licenses/by- nc/4.0/). Non-commercial uses of the work are permitted, provided the original work is properly cited. http://jad.tums.ac.ir/ https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/ J Arthropod-Borne Dis, June 2021, 15(2): 143–151 MR Razavi et al.: Human Cutaneous … 144 http://jad.tums.ac.ir Published Online: June 30, 2021 mon form of leishmaniasis and causes skin le- sions, mainly ulcers, on exposed parts of the body, leaving life-long scars and serious dis- ability or stigma. About 95% of CL cases oc- cur in the Americas, the Mediterranean basin, the Middle East and Central Asia. In 2018 over 85% of new CL cases occurred in 10 coun- tries: Afghanistan, Algeria, Bolivia, Brazil, Co- lombia, Iran (Islamic Republic of), Iraq, Paki- stan, the Syrian Arab Republic and Tunisia. It is estimated that between 600000 to 1 million new cases occur worldwide annually (5-6). Cu- taneous leishmaniasis (CL) is a vector borne disease predominantly found in tropical and subtropical countries. It is an important infec- tious disease in the Eastern Mediterranean countries, including Iran. In the Middle East, cutaneous form is more common than visceral leishmaniasis (VL), and roughly 70–75% of CL incidence is reported from six countries: Afghanistan, Algeria, Brazil, Colombia, Iran (Is- lamic Republic), and the Syrian Arab Republic (7-11). Some vector borne diseases are endemic in Iran and neighboring countries, but the most I important of them is leishmaniasis (12). Re- searchers in Iran have conducted several epi- demiological studies on leishmaniases since 1941 (5). CL is neglected tropical diseases and cause by various types of intracellular proto- zoan species of the genus Leishmania. Iran is endemic for old world CL and CL is one of the differential diagnosis for chronic skin diseases (5-6). Two type of CL is endemic in Iran as Zoonotic Cutaneous Leishmaniasis (ZCL) and Antheroponotic Cutaneous Leishmaniasis (ACL). ZCL is causes by Leishmania major and ACL is cause by Leishmania tropica. Main type the disease (more than 85%) is ZCL in Iran (5). Phlebotomus papatasi has been identi- fied as main vector for ZCL in different parts of Iran (8, 13, 14) and also the rodents of Rhombomys opimus, Meriones libycus, Tatera indica, Nesokia indica, and Meriones hurrianae gerbils are repeatedly reported to be infected with L. major in different endemic foci of ZCL and act as reservoirs (8, 13, 15-16). In some different places of 18 endemic provinc- es transmitting the ZCL especially in rural ar- eas. Phlebotomus sergenti as well as humans and dogs serve as the vectors and reservoirs of ACL (8, 13). Three main district that where transmitting the ACL are Mashhad (in Khora- san Province), Kerman and Bam (in Kerman Province) that almost all of cases in this dis- tricts are ACL, except traveled cases. Alt- hough in some cities a small number of ACL are transmited as Neyshaboor, Sabzevar, Tay- bad, Ghom, Shiraz, Isfahan, Yazd, Kashan, Zahedan and Abadan districts. Dependent to national guideline, diagnosis the cases depend- ent to epidemiological criteria, clinical criteria and laboratory test including confirmation of amastigote forms of Leishmania parasites using direct examination with light microscope with high magnification (1000X), and conduct the standard treatment for confirmed cases, these activities needs for surveillance and CL con- trol (17-19). Based on description of the legal activities of the Ministry of Health and Medi- cal Education In Iran for control the diseases (20) as CL, stablished the diagnostic and treat- ment centers in endemic districts from 2008, in this centers available facilities for Giemsa stain and medicine for diagnosis suspected cas- es and standard treatment the cases free of charge dependent to CL national guide line. And also the effective reservoir and vector control and training population about personal protection and intersectoral cooperation has been explained in national guideline (19, 21). Despite the im- plementation of an effective program for con- trolling CL in Iran the burden of the diseases are still high in some areas of country (22). Due to strengthen activities for CL control in Iran, WHO supported the implementation of the training courses for health staff in Eastern Med- iterranean Region countries (23). Many studies have been conducted on the causes of the spread, increase and outbreak of CL in Iran, which have shown that vegetation cover, climatic factors, disasters and population movement play an im- portant roles in this regard (24-29). In addi- http://jad.tums.ac.ir/ J Arthropod-Borne Dis, June 2021, 15(2): 143–151 MR Razavi et al.: Human Cutaneous … 145 http://jad.tums.ac.ir Published Online: June 30, 2021 tion, to control the disease while taking spe- cial measures in native areas, it is very im- portant to identify high-risk areas to prevent the spread of the disease (30-32). Materials and Methods Study area The CL surveillance system in Iran con- ducting in all provinces and coverage all pop- ulation in endemic and non-endemic areas. The population of Iran is 83,992,949 (2019) and the area of Iran is 1,873,959 square kilometers. 18 out of 31 provinces are endemic for CL and around 75% of population in Iran are leaving in CL endemic areas. CL is one of the report- ing diseases from 1977 and the surveillance system covered this disease in Iran. There are surveillance system for case finding, record- ing and reporting and treatment the cases, the strategic plan for CL control, as inter sectoral cooperation, community education, reservoir control, and vector control. CL is endemic in 18 provinces in Iran and some cases diagnosed from non-endemic provinces that had travel to endemic provinces. Study design A retrospective, cross-sectional study was carried out using data from the national leish- maniasis surveillance system. The data used in this study include data that collected in Cen- tre for communicable Diseases Control (CDC) in ministry of health and medical education in Iran. The portal online computerized record- ing system stablished from 2000 for record the information of CL cases in district level, And the information of recorded cases in 2019, evaluate in 2020. The Iranian CDC in Minis- try of Health and Medical education is respon- sible for surveillance and collection of data on communicable diseases from various districts of the country. Leishmaniasis surveillance and control, the Information about CL have been collected over 35 years, from 1983 to 2000 data were recorded and reported in paper for- mat and from 2000 to 2006 based on Epi-info, version 6 software. Online reporting was launched in 2006 for limited districts and after one years the data including microscopical exam as potential tool for the confirmation of all reported cases were gathered online in all districts. The data collected for this survey ob- tained from surveillance system and include; seasonal trend, individual clinical manifesta- tion, geographical information, laboratory data and treatment methods for all cases of CL. Case definitions were based on the national CL control guideline (19). The zoonosis control de- partment was subset of the center for com- municable diseases control and information for CL were accessed and analyzed by this depart- ment. Ethical approval for the study was ob- tained from the national leishmaniasis expert committee. Statistical analysis The data were analyzed using Microsoft Ex- cel 2013 at the zoonosis control management in Centre for communicable Diseases Control (CDC). Results Iran has been reported an endemic area for CL in the world. In this Report, we describe some CL indicators in Iran. After the earth- quake in bam district in 2003 number of cases increase from average 400 cases per year be- fore earthquake to 3125 cases in 2006, in this district in 2006 with support the national com- mittee revised the national plan for surveil- lance and control the CL in Iran, and stab- lished in Bam district. After 1 year evaluated the results of activities and the national plan conducted in all provinces. The main activi- ties in national plane are: education health per- sonals, intersectoral cooperation, established leishmaniasis diagnosis and treatment center in endemic districts, community education, en- vironment sanitation, vector control and reser- voir control. In CL diagnosis and treatment centers, the facilities for diagnosis and medi- cine for treatment the cases stablished. http://jad.tums.ac.ir/ J Arthropod-Borne Dis, June 2021, 15(2): 143–151 MR Razavi et al.: Human Cutaneous … 146 http://jad.tums.ac.ir Published Online: June 30, 2021 Table 1. Prevalence of CL in different provinces of Iran No Endemic Provinces Geographical zones CL Number CL Incidence rate/100000 1 Semnan Center, East 719 95.9 2 Ilam West, South 470 78.7 3 Golestan North, East 1188 60.9 4 Isfahan North, Center 3127 59.1 5 Fars All 2002 40.0 6 Khorasan-Shomali South 214 24.0 7 Khorasan-Razavi All 1581 23.4 8 Yazd All 260 21.4 9 Ghom Center 293 21.3 10 Khoozestan All 1013 20.7 11 Kerman Center, South 565 17.1 12 Systan va Bloochestan East, South, West 357 12 13 Hormozgan West, South, West 160 8.4 14 Kermanshah West 117 5.9 15 Khorasan-Jonoobi East 39 4.8 16 Lorestan South-west 69 3.8 17 Tehran South 434 3.1 18 Booshehr All 28 2.3 Fig. 1. Trend of cutaneous leishmaniasis Iran 1983–2019 http://jad.tums.ac.ir/ J Arthropod-Borne Dis, June 2021, 15(2): 143–151 MR Razavi et al.: Human Cutaneous … 147 http://jad.tums.ac.ir Published Online: June 30, 2021 Fig. 2. Number of C.L cases by month 2019 Fig. 3. Location of C. Leishmaniasis lesions Iran 2019 http://jad.tums.ac.ir/ J Arthropod-Borne Dis, June 2021, 15(2): 143–151 MR Razavi et al.: Human Cutaneous … 148 http://jad.tums.ac.ir Published Online: June 30, 2021 Fig. 4. Number of C. Leishmaniasis lesions Iran 2019 Fig. 5. Size of C. Leishmaniasis lesions Iran 2019 Trend and distribution In 2019, 13124 CL cases were reported in Iran (Incidence rate 15.8 cases per 100000 pop- ulation). In 2008, 23202 cases reported (Inci- dence rate 32 cases per 100000 population) and in this year stablished new surveillance sys- tem. And dramatically decreased the cases dur- ing 12 years. During this year’s we had two pike in 2014 with 22099 cases and in 2018 with 15714 cases (Fig. 1). In 2019, 12636 (96%) of cases reported from 18 endemic provinces and 488 (4%) of cases reported from non-endemic provinces that have traveled to endemic provinces. More cases reported from Isfahan Province in cen- ter in Iran with 3127 cases and 51.2 incidence rate per 100000. But highest incidence rate was in Semnan Province with 95.9 per 100000 pop- ulation and 719 cases. CL is endemic in 18 out http://jad.tums.ac.ir/ J Arthropod-Borne Dis, June 2021, 15(2): 143–151 MR Razavi et al.: Human Cutaneous … 149 http://jad.tums.ac.ir Published Online: June 30, 2021 of 31 provinces and in tab 1 show the number and incidence rate per 100000 of CL in en- demic provinces. Seasonal aspects Because more than 85% of cases are Zo- onotic in Iran more cases reported from Sep- tember to December (Fig. 2). Clinical aspects The cutaneous lesions were mostly on the hand (62%) and foot (26%) and face (21%). In 1177 cases (9%) two or more organ were infected (Fig. 3). In 46% of cases had one le- sions, and 54% of cases had two or more le- sions, 18 cases had more than 21 cases. And maximum number of lesions was 30 lesions (Fig. 4). Diagnosis the cases in early stage is very important because response to treatment is more effective. And the scar gets smaller. The Fig. 5 show the maximum size of the lesions in CL cases and 85% have the 3cm or bellows the diameter. Conclusions Our study has provided available infor- mation on CL in 2019 in Iran. The review shows CL is endemic in various parts of 18 provinces in Iran and also explain the main clinical manifestation. Using national CL con- trol guideline was effective to decreasing dra- matically number of cases in recent years but Population how are leaving in endemic areas are at risk and also population in other areas is also at risk to take infection if travel to en- demic areas. Activities for control the CL in national guideline needs to fallows but it de- pendent to budget, and unfortunately it is not possible to cover all endemic areas. Also in non-endemic areas with appropriate climate factors and plants conditions and environment sanitation, that increase population of rodent and sand-flies are high risk areas that CL pre- sent in this non endemic places. 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