J Arthropod-Borne Dis, Sep 2022, 16(3): 180–195 M Khoobdel et al.: Scabies as a … 180 http://jad.tums.ac.ir Published Online: Sep 30, 2022 Review Article Scabies as a Neglected Tropical Disease in Iran: A Systematic Review with Meta-Analysis, during 2000–2022 *Mehdi Khoobdel1, Shahyad Azari-Hamidian2,3, Ahmad Ali Hanafi-Bojd4,5, Hasan Bakhshi6, Amirsajad Jafari7, Mohammad Moradi1 1Health Research Center, Lifestyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 2Research Center of Health and Environment, School of Health, Guilan University of Medical Sciences, Rasht, Iran 3Department of Medical Parasitology, Mycology and Entomology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran 4Department of Medical Entomology and Vector Control, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 5Zoonoses Research Center, Tehran University of Medical Sciences, Tehran, Iran 6Vector-borne Diseases Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran 7Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran *Corresponding author: Dr Mehdi Khoobdel; E-mail: khoobdel@yahoo.com (Received 25 June 2022; accepted 31 Aug 2022) Abstract Background: Scabies is referred to the infestation of skin by an ectoparasite, Sarcoptes scabiei. Having considerable financial consequences, this disease is a public health concern in several countries. In this review, we aimed to deter- mine the current status of scabies in different provinces of Iran. Methods: Google Scholar, PubMed, Scopus, Science Direct, Scientific Information Database (SID), Sci-explore, Civil- ica, Magiran, Iranian Research Institute for Information Science and Technology and Elmnet databases were searched to find the related data in the time period within 2000–2022. To have a better insight into the status of prevalence of sca- bies in Iran, a meta-analysis and meta-regression was performed. Results: A total of 943 relevant studies were retrieved from the databases, and 62 eligible studies met all the needed criteria for inclusion in this systematic review. Scabies was investigated and reported in at least 22 and 21 provinces of Iran respectively. Most of the studies were conducted in Tehran, Razavi Khorasan, Hormozgan, Fars and Guilan Prov- inces. Positive samples of scabies belonged to humans, sheep, goats, dogs, rabbits, mice and gazelles. Meta-analysis showed that the overall estimated presence of scabies in Iran during 2000–2022 was 7% (95% CI 4.7–10.3%, P< 0.001). Conclusion: Infestations due to S. scabiei in Iran occur in different geographical locations and different climates. As a neglected tropical disease, the literature about the burden of scabies in Iran is inadequate. The present review highlights the importance of development of comprehensive strategies for the diagnosis and control of scabies, especially the prov- inces with high infestation rates. Keywords: Scabies; Sarcoptosis; Sarcoptes scabiei; Ectoparasites; Iran Introduction Ectoparasites, such as fleas, lice, ticks and some species of mites, flies and hemipteran bugs, use vertebrates as feeding and breeding grounds to survive and complete their life cy- cles. Scabies, caused by an obligate microscopic parasitic mite, Sarcoptes scabiei (Linnaeus, 1758) (Acarina: Sarcoptidae), also named sar- coptic mange in cases referring to animals, is a contagious and common skin parasitic disease (1). The members of the genus Sarcoptes gen- erally are referred to as scabies mites. Scabies is also known as sarcoptosis based on the standardized nomenclature for parasitic dis- eases (SNOPAD) (2). Scabies is considered to Copyright © 2022 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, Sep 2022, 16(3): 180–195 M Khoobdel et al.: Scabies as a … 181 http://jad.tums.ac.ir Published Online: Sep 30, 2022 be a neglected ectoparasite progressing to sec- ondary bacterial skin infection that may lead to serious complications including septicemia, renal disease and rheumatic heart disease, re- sulting from the burrowing of S. scabiei in the epidermis of humans and animals (3). Adult S. scabiei digs burrow tunnels and lays 2 to 3 eggs each day. Despite several reports of sca- bies in different countries, little is known about the biology and host-parasite interactions of S. scabiei (4). The disease is spread around the world and is a public health concern in several countries and is mainly related to poverty and overcrowd- ing. More than 200 million people all around the world suffer from scabies (5). Global prev- alence estimate ranges from 0.2% to 71% with an average of 5–10% in children. Meanwhile, S. scabiei infects more than 100 mammalian species, including domestic animals, leading to cross-species transmission (6). Scabies covers a wide range of clinical manifestations, present- ing three main forms: classic, nodular, and con- tagious crusted variant also called Norwegian scabies, containing millions of S. scabiei on a single infested individual (7). Scabies is a dis- ease of public health importance and is for- mally designated as a neglected tropical dis- ease (NTD) by World Health Organization (WHO) in 2017, to encourage the efforts for its eradication (8). Having considerable financial consequenc- es, this disease is a public health concern for un- derprivileged communities in several low and middle-income countries, and also in some de- veloped countries (9). Transmission of S. sca- biei occurs through skin-to-skin contact with a person who is infested with the mite. This skin disease is more prevalent among vulner- able groups such as children and young peo- ple (7). People infested with S. scabiei require rapid identification and treatment, as a misdi- agnosis subsequently may lead to an outbreak and an increased economic burden (10). Infes- tation in the elderly and people with immuno- deficiency disorders often manifests as gen- eral dermatitis that affects many parts of the body, accompanied by scaling and sometimes blistering and cracking of the skin. Scabies is usually transmitted through close contact with an infected person. The disease is more com- mon among people that are forced to live to- gether as a group. Different studies have shown a significant relationship between the preva- lence of the disease and densely populated ar- eas (11). Hence, the spread of this ectoparasite is more likely in crowded families, soldiers, and school children. Less frequently, contaminated clothing and bedding can transmit the mite to other people. To date, different studies have shown the prevalence of scabies in Iran. However, a com- prehensive review and analysis on published data seems to be essential in order to have a better insight on the distribution of scabies in different hosts in all provinces of Iran, to un- derstand the latest situation of the disease in the country, and development of a national pro- gram by health authorities for regular diagno- sis and control of the disease in provinces with high infestation rates. In this systematic re- view and meta-analysis, the latest available lit- erature on the prevalence of S. scabiei in hu- mans and hosts in different provinces of Iran was investigated. Materials and Methods Searching strategy The present systematic review and meta- analysis was accomplished on the basis of the Preferred Reporting Items for Systematic Re- views and Meta-analyses (PRISMA) statement. A comprehensive literature search was conduct- ed using databases: Google Scholar, PubMed, Scopus, Science Direct, Scientific Information Database (SID), Sci-explore, Civilica, Magiran, Iranian Research Institute for Information Sci- ence and Technology and Elmnet from 2000 until May 2022. Selected keywords used for the search were based on previously published stud- ies comprising: scabies, Sarcoptes scabiei and http://jad.tums.ac.ir/ J Arthropod-Borne Dis, Sep 2022, 16(3): 180–195 M Khoobdel et al.: Scabies as a … 182 http://jad.tums.ac.ir Published Online: Sep 30, 2022 Iran. In addition, all provinces of Iran were searched specifically with a similar protocol. The search was conducted in both English and Persian languages with similar keywords. Paper selection Studies’ Quality assessment were developed according to CoCoPop structure [Co (Condi- tion)= infestation by mites; Co (Context)= prov- inces of Iran; Pop (Population)= animals and human]. Inclusion and exclusion criteria Author’s names, publication year, host, ge- ographical region, positive samples and sam- ple sizes were retrieved and then added to pre- designed forms. All animal and human studies reporting infestation with the mite in different parts of Iran with respect to publication year were included. Papers with no full-text avail- ability, from other countries, review articles, unpublished data, as well as studies conducted before 2000 were excluded. Meta-analysis and meta-regression Random Model was used to calculate pooled prevalence with 95% confidence in- tervals. Cochran Q test (P< 0.05 shows statis- tically significant heterogeneity) and I2 test [< 25% (low), 30% < x < 60% (moderate), and > 75% (high) heterogeneity] were used to deter- mine heterogeneity. Also, a forest plot was em- ployed to visualize the heterogeneity among the studies. In addition, heterogeneity was ex- plored through meta-regression using some mod- erators. Egger’s and Begg's tests (P> 0.05 indi- cate a reasonable publication bias) as well as Funnel plot and Trim and Fill test were ap- plied to investigate the publication bias. The subgroup analysis was conducted according to the publication year, host and geographical lo- cation. In this meta-analysis, each row of Ta- ble 1 was considered a separate study. Data were analyzed with Comprehensive Meta-Analysis Version 3 Software (Biostat, USA). Results Search output A total of 943 relevant studies were re- trieved from the databases, of which 140 stud- ies were screened and 132 full-text articles were assessed for eligibility. Furthermore, 62 eligi- ble studies met all the needed criteria for in- clusion in this systematic review. In the final step, 44 studies were included in the meta- analysis (Fig. 1). Our results show that during the period of 2000 to 2022, scabies was stud- ied and reported in humans, sheep, dogs, goi- tered gazelles (Gazella subgutturosa), white rabbits, house mice, and second-hand clothes, in at least 22 and 21 provinces, respectively. Most of the studies were conducted in Tehran (10), Razavi Khorasan (8), Hormozgan (6), Fars (6) and Guilan (5) Provinces (Table 1). The studied provinces included Tehran (10 studies, reporting scabies in humans, sheep, dogs and second-hand clothes), Razavi Khorasan (8 studies, reporting scabies in humans, sheep and dogs), Hormozgan (6 studies, reporting scabies in human), Fars (6 studies, reporting scabies in humans and dogs), Guilan (5 studies, reporting scabies in humans and dogs), Isfahan (4 stud- ies, reporting scabies in humans), Khuzestan (4 studies, reporting scabies in humans and dogs), West Azerbaijan (4 studies, reporting scabies in humans, sheep, goats and white rabbits), Ma- zandaran (4 studies, reporting scabies in hu- mans and dogs), Bushehr (3 studies, reporting scabies in humans and goitered gazelles), Ker- manshah (3 studies, reporting scabies in humans and dogs), Kerman (3 studies, reporting sca- bies in humans and house mice), Hamadan (3 studies, reporting scabies in humans), Alborz (2 studies, reporting scabies in humans), East Azerbaijan (2 studies, reporting scabies in hu- mans and white rabbits), Ardabil (1 study, re- porting scabies in humans), Qazvin (1 study, no evidence of scabies in dogs), Golestan (1 study, reporting scabies in humans), Kurdi- stan, Lorestan, Qom, and Sistan and Baluchi- stan (1 study, reporting scabies in humans), and http://jad.tums.ac.ir/ J Arthropod-Borne Dis, Sep 2022, 16(3): 180–195 M Khoobdel et al.: Scabies as a … 183 http://jad.tums.ac.ir Published Online: Sep 30, 2022 two studies in the country without specifying the details of the rates of infestation in each province, where the positive cases of humans were found. On the other hand, the status of mite infestation was not clear in Chahar Ma- hal and Bakhtiari, Ilam, North Khorasan, South Khorasan, Zanjan, Semnan, Kohgiluyeh and Boyer-Ahmad, Yazd, Qazvin and Markazi Prov- inces (Fig. 2). Pooled effect size, heterogeneity and bias me- ta-analysis Random effect model showed that the to- tal prevalence of mite infestation in Iran dur- ing 2000–2022 was 7% (95% CI 4.7%–10.3%, P< 0.001). A forest plot determined the preva- lence of infestation rate across the country (Fig. 3). Results showed a strong significant heter- ogeneity (Q= 4859.445, df= 47, I2= 99.03%, P< 0.001). Begg and Mazumdar Rank Correlation Test as well as Egger's Test of the Intercept illustrated that the publication bias was not substantial (2-tailed P> 0.05). In line with the results of both Egger and Begg’s tests, Funnel plot showed symmetry in the presence of neg- ligible publication bias (Fig. 4). Duval and Tweedie’s trim and fill test initially trims the asymmetric studies from the left-hand side to locate the unbiased effect (in an iterative pro- cedure), and then fills the plot by re-inserting the trimmed studies on the left as well as their im- puted counterparts to the right of the mean effect. Subgroups’ meta-analysis The subgroup analysis was conducted ac- cording to publication year, host, and geograph- ical location (Table 2). In terms of publication year, subgroup meta-analysis indicated a high- er prevalence of infestation in published liter- ature from 2015 until the present time (8.1% 95% CI: 0.046–0.139) in comparison to years before this time point (6.2%; 95% CI: 0.037– 0.103). Location-based analysis suggests that the highest (14.6%; 95% CI: 0.072–0.272) and lowest (3.9%; 95% CI: 0.025–0.059) prevalence belonged to south and north, respectively. Hosts’ subgroup analysis showed the prevalence of in- festation was higher among animal (8.5%; 95% CI: 0.053–0.134) in comparison to human cas- es (6.2%; 95% CI: 0.036–0.104). Meta-regression analysis A meta-regression was performed, pooling all studies across location (geographical lati- tude), publication year, and sample sizes. A significant heterogeneity was associated with sample size, according to the method of the mo- ments test (P= 0.000), with a R2 of 39% (Fig. 5). In terms of publication year, method of mo- ments showed that some heterogeneity can al- so be related to the publication year (R2= 13%; P= 0.133), however this was not statistically sig- nificant. An increase in the publication year was in line with an increase in the prevalence, which indicates that recently published studies had re- ported higher infestation rates in comparison to older ones (but this relationship was not al- so statistically significant) (Fig. 5). Maximum likelihood model was assessed to perform the meta-regression for the location moderator and the geographical latitude. R2 showed that a very small heterogeneity might be justified due to latitude. Though, this was not statistically sig- nificant (4%; P= 0.06). Table 1. Details of investigations carried out and reported the occurrence of scabies in Iran, during 2000–2022 Province Description Prevalence Host Year Reference (s) Positive/Total (%) 1 Alborz Prevalence of scabies among prisoners 31/1404 2.2 Human 2006 (12, 13) 2 Ardabil Frequency of scabies# 51/NA NA Human NA (14) 3 Azerbaijan, East Ectoparasites of white rabbits 9/50 18 White rabbit 2020 (15) A case of scabies in a sheepherder* 1/1 100 Human 2014 (16) http://jad.tums.ac.ir/ J Arthropod-Borne Dis, Sep 2022, 16(3): 180–195 M Khoobdel et al.: Scabies as a … 184 http://jad.tums.ac.ir Published Online: Sep 30, 2022 Table 1. Continued ... 4 Azerbaijan, West Ectoparasites of white rabbits 9/50 18 White rabbit 2020 (15) Ectoparasites of sheep and goat flocks 2/77 2.6 Sheep 2006 (17) Ectoparasites of sheep and goat flocks 0/119 0 Goat 2006 (17) Scabies among police forces # NA/NA NA Human 2002 (18) Ectoparasites of goats 12/403 2.97 Goat 2011 (19) 5 Bushehr Study on the sarcoptic mange of gazelle 7/8 87.5 Gazella sub- gutturosa 2007 (20) Scabies in primary schools 84/3913 2.14 Human 2001 (21) Scabies among police forces # NA/NA NA Human 2002 (18) 6 Fars A 40-year-old man* 0/1 0 Human 2021 (22) Scabies in HIV/AIDS Indi- viduals 4/240 1.66 Human 2018 (23) Scabies in people 51/203 25.12 Human 2012 (24) A case of crusted scabies* 1/1 100 Human 2018 (25) A case with low-vision prob- lem* 0/1 0 Human 2021 (22) Scabies in dogs 16/16 100 Dogs 2005 (26) 7 Golestan Scabies among primary school children # NA/NA NA Human 2001 (27) 8 Guilan Ectoparasites of Stray Dogs* 1/35 2.85 Dog 2016 (28) Prevalence of skin diseases among prisoners 95/2100 4.5 Human 2003 (29) Scabies among police forces# 194/NA NA Human 2002 (18) Scabies among primary school children 50/3656 1.36 Human 2003 (30) Skin disorders among elder patients 19/440 4.31 Human 2013 (31) 9 Hamadan Prevalence of scabies among prisoners 10/384 2.6 Human 2015 (32) Parasitic investigation among patients 0/124 0 Human 2006 (33) Scabies in West of Iran# 7/NA NA Human 2014 (34) 10 Hormozgan Study on primary school chil- dren 15/480 3.1 Human 2021 (35) Prevalence of scabies among prisoners 38/67 56.71 Human 2007 (36) Cases of skin diseases were studied 277/6841 4.04 Human 2005 (37) Prevalence of scabies in sol- diers 95/763 12.45 Human 2002 (38) Scabies among police forces # 262/NA NA Human 2002 (18) Scabies in human community # 122/NA NA Human 2018 (39) 11 Isfahan An 85-year-old man* 1/1 100 Human 2021 (40) A family, all infected 5/5 100 Human 2018 (41) Scabies in patients 817 /2899 28.18 Human 2009 (42) Scabies in patients 28/129 21.7 Human 2017 (43) 12 Kerman Scabies in patients # NA/87 NA Human 2017 (44) Prevalence of scabies among prisoners 32/2851 1.12 Human 2000 (45) Scabies in house mouse 2/2 100 Mus muscu- lus 2018 (46) http://jad.tums.ac.ir/ J Arthropod-Borne Dis, Sep 2022, 16(3): 180–195 M Khoobdel et al.: Scabies as a … 185 http://jad.tums.ac.ir Published Online: Sep 30, 2022 13 Kermanshah Ectoparasites fauna of dogs 21/137 15.33 Dog 2017 (47) Scabies in HIV infected pris- oners 9/79 11.39 Human 2003 (48) Scabies in West of Iran# 170/NA NA Human 2014 (34) 14 Khuzestan Two cases of Norwegian sca- bies 2/2 100 Human 2019 (49) Severe case in a 4 month old child* 1/1 100 Human 2008 (50) Scabies among police forces# 263/NA NA Human 2002 (18) Scabies in companion dogs 7/126 5.55 Dog 2012 (51) 15 Kurdistan Scabies among police forces# NA/NA NA Human 2002 (18) 16 Lorestan Scabies among police forces# NA/NA NA Human 2002 (18) 17 Mazandaran Ectoparasites of stray dogs 2/15 13.33 Dog 2016 (28) Scabies in primary school children 225/10737 2.09 Human 2003 (52) Scabies among patients 89/1140 7.8 Human 2007 (53) Groin pruritus in female pa- tients 1/115 0.8 Human 2010 (54) 18 Qazvin Ectoparasites of stray dogs 0/20 0 Dog 2016 (28) 19 Qom Scabies among patients 68/411 16.54 Human 2015 (55) 20 Razavi Khorasan Suspected patients 375/ 1814 20.67 Human 2014 (56) Infestation in dogs 10 /460 2.17 % Dog 2020 (57) Scabies in a herd of sheep 10/75 13.33 Sheep 2008 (58) Genital dermatoses 36/355 10.1 Human 2016 (59) Scabies among police forces # NA/NA NA Human 2002 (18) A case of disseminated sca- bies infection* 1/1 100 Human 2005 (60) Scabies in a rehabilitation center 21/110 19.09 Human 2019 (61) Dermatological study on do- mestic doges 17/316 5.06 Dog 2013 (62) 21 Sistan and Baluchistan Scabies among police forces# NA/NA NA Human 2002 (18) 22 Tehran Prevalence of skin related diseases 26/3120 0.83 Human 2021 (63) Study on dermatological emergencies 132 /2539 5.2 Human 2017 (64) Study on sheep sarcoptic mange 278/ 5603 4.96 Sheep 2009 (65) Infestation in dogs 37/143 25.9 Dog 2012 (66) Scabies among police forces # NA/NA NA Human 2002 (18) A case of crusted scabies * 1/1 100 Human 2020 (67) Ectoparasites of second-hand clothes 6/800 0.75 NA 2021 (68) A case of Norwegian scabies* 1/1 100 Human 2002 (69) A case of scabies* 1/1 100 Human 2006 (70) A case of crusted scabies with brain astrocytoma* 1/1 100 Human 2010 (71) 23 Iran Scabies among soldiers 66/58850 0.11 Human 2003 (72) Scabies in Iran’s Army 5277/NA# NA Human 2014 (73) *: These studies were not included in the meta–analysis due to the sample size less than 2 #: These studies were not included in the meta–analysis due to the insufficient data Table 1. Continued ... http://jad.tums.ac.ir/ J Arthropod-Borne Dis, Sep 2022, 16(3): 180–195 M Khoobdel et al.: Scabies as a … 186 http://jad.tums.ac.ir Published Online: Sep 30, 2022 Fig. 1. Flowchart of the data selection in terms of Sarcoptes scabiei infestation in Iran, during 2000–2022 Fig. 2. Human cases of scabies reported in different provinces of Iran; Further to investigations conducted during 2000–2022, scabies has been reported in humans in at least 21 provinces http://jad.tums.ac.ir/ J Arthropod-Borne Dis, Sep 2022, 16(3): 180–195 M Khoobdel et al.: Scabies as a … 187 http://jad.tums.ac.ir Published Online: Sep 30, 2022 Table 2. Prevalence of Sarcoptes scabiei infestation in Iran according to year, host, and location, during 2000–2022 Subgroup variable Number of studies Prevalence (95% CI) I2 (%) Heterogeneity (Q) P value Location North 16 0.039 (0.025–0.059) 97.431 583.954 0.195 South 11 0.146 (0.072–0.272) 98.026 506.709 0.000 West 9 0.059 (0.029–0.118) 87.016 61.614 0.000 East 6 0.097 (0.051–0.177) 95.202 104.218 0.000 Center 6 0.142 (0.011–0.716) 99.784 2310.669 0.000 Host Human 30 0.062 (0.036–0.104) 99.349 4453.800 0.000 Animal 18 0.085 (0.053–0.134) 94.052 285.794 0.000 Year 2015 30 0.062 (0.037–0.103) 99.357 4511.214 0.000 2015 18 0.081 (0.046–0.139) 94.679 319.480 0.000 Fig. 3. Forest plot of the prevalence of Sarcoptes scabiei infestation in Iran during 2000–2022; Total prevalence of mite infestation in Iran during 2000–2022 was 7% (95% CI 4.7%–10.3%, P< 0.001) http://jad.tums.ac.ir/ J Arthropod-Borne Dis, Sep 2022, 16(3): 180–195 M Khoobdel et al.: Scabies as a … 188 http://jad.tums.ac.ir Published Online: Sep 30, 2022 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 0.0 0.5 1.0 1.5 2.0 S ta n d a rd E rr o r Logit event rate Funnel Plot of Standard Error by Logit event rate Fig. 4. Funnel plot of standard error by logit event rate for Sarcoptes scabiei infestation in Iran during 2000–2022; Most of the studies are distributed at the top of the graph in a balanced way, which indicates a negligible publication bias Fig. 5. Meta-regression chart showing the logic event rate of Sarcoptes scabiei infestation in Iran according to sample size during 2000–2022; A significant heterogeneity was associated with sample size (the number of mites) http://jad.tums.ac.ir/ J Arthropod-Borne Dis, Sep 2022, 16(3): 180–195 M Khoobdel et al.: Scabies as a … 189 http://jad.tums.ac.ir Published Online: Sep 30, 2022 Discussion Scabies caused by S. scabiei may be one of the first reported human diseases with a well-known etiology (74). Such an infestation significantly impacts the quality of life in vul- nerable people with adverse sequelae, especially in low-resource settings (9). To our knowledge, the present meta-analysis is the first large-scale study that examined the prevalence of scabies in different provinces in Iran. Further to our review, the occurrence of scabies has been re- ported in at least 21 provinces out of 31 prov- inces. Pooled prevalence of mite infestation in Iran was calculated as 7% (95% CI 4.7%–10.3%, P< 0.001). Meanwhile, the subgroups’ meta- analysis showed that the prevalence of infes- tation was higher in the south (14.6%; 95% CI: 0.072–0.272) and center [14.2%, 95% CI: 0.011–0.716] of Iran. Also, meta-regression anal- ysis suggested that lower latitude have higher prevalence of mite infestation, suggesting that the humidity and climate may be associated with the spread of S. scabiei (but the latter result was not statistically significant). A previous in- vestigation has shown that the mites have bet- ter survival and fertility rates in humid condi- tions (75); However, some other studies have concluded that cold weather favors the popu- lation dynamic of mites (76, 77). Meta-regres- sion illustrated that an increase in the publica- tion year was in line with an increase in the prevalence which indicates that recently pub- lished studies had reported higher infestation rates in comparison to older ones. This may be justified due to the improvements in the knowledge of health workers or health system. During the period of the present review (2000–2022), scabies was recorded in humans, sheep, dogs, goitered gazelles, white rabbits, house mice and second-hand clothes in Iran; however, there are some records of scabies in cattle, cats, horses and pigs in older documents (78). Also, there are few unpublished documents on scabies in camels in the country (79). In the present study, based on the searching criteria and the eligible documents, the presence of sca- bies was shown in 21 provinces of Iran (out of 31); thus, there were not eligible documents for final analysis for 10 remaining provinces in- cluding Chahar Mahal and Bakhtiari, Ilam, North Khorasan, South Khorasan, Zanjan, Semnan, Kohgiluyeh and Boyer-Ahmad, Yazd, Qazvin and Markazi. On the other hand, there are some documents on the occurrence of scabies in some of the aforementioned provinces such as Ilam (80), Qazvin (79) and Zanjan (73) that did not meet our criteria. Following by an increased occurrence of scabies in some countries in Europe, Asia and Africa, scabies cases have recently been in- creased in Turkey (81) and Saudi Arabia (82). In contrast with the results of our meta-regres- sion analysis, in Turkey, located in the north- west of Iran, the prevalence of scabies was re- ported as 10.9%, showing that there was an increase in the cases of scabies both before and during the COVID-19 pandemic. This situation was considered an epidemic of scabies (83, 84). Studies on scabies during the COVID-19 pan- demic in Iran was limited to a few investiga- tions (published during the pandemic), show- ing a prevalence of 0.83% in patients referred to a hospital in Tehran (63), 0.75% in second- hand clothes studied in Tehran (68), and 3.1% in primary school children in Hormozgan (35), suggesting that the pandemic has not resulted in a higher frequency of scabies compared to former investigations. In Iraq, Alsamarai (2008) has reported sca- bies in a dermatology clinic in Tikrit with a fre- quency of 1.1% among 1,194 studied patients. Among the positive cases, prisoners were iden- tified as the high-risk group (85). Different stud- ies have shown that scabies is more frequent among prisoners in Iran with 56.71% in Hor- mozgan (36), 2.2% in Alborz (12, 13), 11.39% in Kermanshah (HIV infected) (48), 1.12% in Kerman (45), 4.5% in Guilan (29) and 2.6% in Hamadan (32) Provinces. Furthermore, a study http://jad.tums.ac.ir/ J Arthropod-Borne Dis, Sep 2022, 16(3): 180–195 M Khoobdel et al.: Scabies as a … 190 http://jad.tums.ac.ir Published Online: Sep 30, 2022 carried out on the incidence of scabies in 1,300 displaced people who visited the dermatology clinics and health care centers in Duhok Gov- ernorate, located in the Kurdistan Region of Iraq bordered with Kermanshah and Kurdistan Provinces of Iran, the prevalence of scabies was reported in 45% of studied people (86). In Saudi Arabia, located in the south of Iran, high temperature is explored as a leading fac- tor for the occurrence of scabies (87). In Iran, Khuzestan, Bushehr and Hormozgan are among the provinces with a high temperature. The prev- alence of scabies in Khuzestan Province in com- panion dogs has been reported as 5.55% (51). Furthermore, in Hormozgan Province, the prev- alence of scabies among primary school chil- dren, prisoners, people with skin diseases, and soldiers, have been reported as 3.1% (35), 56.71% (36), 4.04% (37) and 12.45%, respec- tively (38). In Bushehr Province, an investiga- tion on gazelles (Gazella subgutturosa) showed that 7 of 8 studied animals were infested with S. scabiei (20). Another study showed that 2.14% of 3,913 of primary school children in this province were positive for S. scabiei (21). Previous findings in Pakistan have identi- fied "inadequate bathing", "infrequent chang- ing of clothes", "low education", "sharing beds, clothes, towels" and "being away from the bar- racks" as the most important risk factors for scabies (88). Prevalence of scabies in soldiers has been studied in some provinces of Iran: Soleymani Ahmadi et al. (38) have reported a prevalence of 12.45% in 763 studied soldiers in Hormozgan Province. Another large-scale investigation on 58,850 soldiers conducted in Iran showed a prevalence of 0.11% (72). Mean- while, 5,277 positive cases among Iran’s army (the prevalence rate was not identified) were reported in 2014 (73). In another investigation carried out by Tufail and Khan in 2021 on pa- tients who visited a hospital in Pakistan, they showed that the risk of scabies was higher in crowded places. Furthermore, the risk was low- er in people having acceptable living and hy- giene conditions (89). Meanwhile, molecular analysis of S. scabiei in Pakistan has shown the presence of different varieties of mites in differ- ent hosts and different geographic regions (90), suggesting the possibility of the occurrence of different varieties of S. scabiei in different re- gions of Iran. In most parts of the meta-analysis the re- sults indicated high heterogeneity (I2> 80%). Subgroup meta-analysis of separate modera- tors, also revealed high heterogeneity. We tried to justify this heterogeneity by meta-regression. Accordingly, it was concluded that almost 50% of the reported heterogeneity might be related to different sample sizes, locations and publi- cation year. Also, some other factors may be the reason behind the high heterogeneity that were not included in this meta-regression (for example different detection methods, popula- tions of interest, and seasons). Publication bias is a considerable problem for the integrity of a meta-analysis, as it illustrates overestimated and underestimated effects. Conclusion With an overall estimated presence of sca- bies in Iran during 2000–2022 as 7% (95% CI 4.7–10.3%, P< 0.001), S. scabiei infestation is considered a health concern. In the first step, di- agnosis and treatment of the infestations caused by this species are among the key factors for pre- vention of its distribution. Meanwhile, scabies is preventable by identification of risk factors that should be characterized in different regions and different groups of people. The literature on the identification of scabies, molecular analysis of S. scabiei collected in different groups of people in different provinces, and the burden of scabies in Iran is not adequate. The present systematic review highlights the need for development of a national program for regular diagnosis of sca- bies in high-risk places such as schools, prisons, and regions with inadequate health facilities, and the importance of adopting effective strategies for control and prevention of scabies in the provinces with high infestation rates. http://jad.tums.ac.ir/ J Arthropod-Borne Dis, Sep 2022, 16(3): 180–195 M Khoobdel et al.: Scabies as a … 191 http://jad.tums.ac.ir Published Online: Sep 30, 2022 Acknowledgements We highly appreciate Dr Zakkyeh Telma- darraiy (TUMS) for her scientific support. 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