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Aghaei Afshar A, Gorouhi M A, Sharifi I, Yousefi S, Shirani-Bidabadi L, Faraji M, et al . Application of Rodenticides for the Control of Zoonotic Cutaneous Leishmaniasis in Iran: A Systematic Review of the Literature. J Environ Health Sustain Dev 2024; 9 (1) :2161-2170
URL: http://jehsd.ssu.ac.ir/article-1-675-en.html
Department of Vector Biology and Control of Diseases, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
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Application of Rodenticides for the Control of Zoonotic Cutaneous Leishmaniasis in Iran: A Systematic Review of the Literature

Abbas Aghaei Afshar 1, 2, Mohammad Amin Gorouhi 1,3, Iraj Sharifi 2, Saideh Yousefi 4, Leila Shirani-Bidabadi 1,3, Maryam Faraji 5, Parya Jangipour Afshar 6, Ismaeil Alizadeh 7, 1*


1 Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran.
2 Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
3 Department of Vector biology and Control, Faculty of Public Health, Kerman University of Medical Sciences, Kerman, Iran.
4 Department of Public Health, Sirjan School of Medical Sciences, Sirjan, Iran.
5 Environmental Health Engineering Research Center, Kerman University of Medical Sciences, Kerman, Iran.
6 Department of Biostatistics and Epidemiology, Faculty of Public Health, Kerman University of Medical Sciences, Kerman, Iran.
7 Department of Vector Biology and Control of Diseases, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
A R T I C L E  I N F O ABSTRACT
ORIGINAL ARTICLE Introduction: Rodent control programs have a long history of controlling zoonotic cutaneous leishmaniasis (ZCL) in Iran. The present systematic review reports the effect of rodenticides in reducing ZCL in Iran. 
Materials and Methods: Various electronic databases were explored for reliable research using appropriate keywords between January 1970 and September 2023. Relevant studies were included based on the inclusion criteria. All articles identified from the systematic search were added into Endnote X9 (Clarivate Analytics) and duplicate articles were removed. This study followed standard procedures for systematic reviews and reported results according to systematic reviews guidelines.
Results: Overall, 637 documents were identified after screening based on the PRISMA checklist, and finally, 13 papers were included in this systematic review. The findings indicated that most of studies used zinc phosphide (2.5%) and Klerat® mixed with wheat grains in rodents control programs in Iran. The results showed that rodent control programs were implemented in five provinces of Iran, including Esfahan, Yazd, Semana, Golestan, Kermanshah, and Fars, with the highest number of studies in Esfahan province. According to results, the incidence rate of ZCL significantly reduced after rodenticide implementation.
Conclusion: This review study provides a better understanding of rodent control programs trends as a promising and practical approach to reducing ZCL incidence in Iran over the past 50 years and can serve as a reference for planning future control and research programs.

Article History:
Received: 03 November 2023
Accepted: 20 January 2024

*Corresponding Author:
Ismaeil Alizadeh
Email:
ismaeil.alizadeh@yahoo.com
Tel:
+98 9168448158

Keywords:
Rodent Control,
Rodenticides,
Zoonotic Cutaneous Leishmaniasis,
Iran.
Citation: Aghaei Afshar A, Gorouhi MA, Sharifi I, et al. Application of Rodenticides for the Control of Zoonotic Cutaneous Leishmaniasis in Iran: A Systematic Review of the Literature. J Environ Health Sustain Dev. 2023; 9(1): 2161-70.
Introduction
Zoonotic cutaneous leishmaniasis (ZCL) is a vector-borne protozoan disease transmitted to humans by the bite of blood-feeding female phlebotomine sand flies 1, 2. This neglected disease is a growing public health concern in many rural areas of Iran, involving 17 out of 31 provinces 2-4.
In endemic locations, controlling ZCL is more challenging. Despite efforts to control this infectious disease, it is still endemic in different countries, including Iran 1. The incidence of ZCL in Iran in 2019 was 15.8 cases per 100,000 people5. One of the effective ways to control ZCL is to eliminate the disease reservoirs in endemic areas 1. Researchers in Iran have used several approaches to control ZCL, including i. Impregnated bed nets and curtains with pyrethroids, ii. Indoor residual spraying, iii. Application of repellents, iv. A rodent control operation, v. Health education to the community, and vi. Leishmanization in an emergency complex situation 6.
Rodents are the primary reservoir hosts of ZCL in the world, as well as Iran 7. They are essential vertebrates belonging to the class Mammalia and the order Rodentia. In addition to being reservoirs, they transmit numerous communicable diseases to humans and livestock 8. Furthermore, several microorganisms such as bacteria, rickettsia, viruses, protozoa, and helminths are transmitted by rodents to humans and livestock 9.
In Iran, four rodent species are known as the principal animal reservoir of ZCL, including Rhombomys opimus (the great gerbil), Meriones libycus (the Libyan Jird), Meriones hurrianae (the desert gerbil), and Tatera indica (the Indian gerbil) 3, 10. Rhombomys opimus has been known as the main rodent reservoir of ZCL in Iran central, north, and northeastern parts 3, 11, 12. Tatera indica, Nesokia indica, and Meriones libycus are known as the main rodent reservoirs of ZCL in the south, west, and southwestern parts of Iran 11.
Rodenticides have been used to control urban gerbils as effective pesticides 13. They are anticoagulant pesticides that are widely used in agricultural and urban rodent control. Several rodenticides, including cereal-based baits, pastes, tracking powders, and wax blocks, are commercially available worldwide for controlling rodents 14.
Rodents control programs have been implemented for many years in Iran and are a promising and practical approach to reduce ZCL incidence in Iran. However, there are significant research gaps in this field, and this study aims to fill these gaps. This study systematically evaluated papers that examined the impact of rodenticides on ZCL control in Iran. The study findings were presented with recommendations for policy, identifying critical gaps in the evidence base, and highlighting future needs for rodent control in the field. To the best of the authors’ knowledge, no comprehensive systematic review has ever been published on rodent control studies in the field, and the present study is the first systematic review to specifically address the implementation of rodent control operation programs in reducing ZCL in Iran. The collected evidence of this systematic review would serve as a basis to guide priorities in focusing rodent control efforts according to different geographic areas of the world, especially in Iran. Moreover, the results of this review can enable health officers to provide appropriate recommendations for rodent control in fields for workers.
Materials and Methods
Data sources and search strategy
The systematic literature search was performed on September 30, 2023.  The search strategy was designed to identify relevant electronic studies published between January 1970 and September 2023. International electronic databases were systematically searched, including Web of Scince, PubMed, Scopus, Google Scholar, and national databases, including Magiran, IranDoc, and Scientific Information Database (SID). The search was performed using medical subject headings (MeSH). Keywords were used to perform the literature search, including (Rodenticides)) OR ((Rodent Control)) AND ((Zoonotic Cutaneous Leishmaniasis)) AND ((Iran)).
Inclusion and exclusion criteria
The inclusion criteria for the current systematic review consisted of i. English and Persian articles (i.e., at least the abstract), ii. Original articles that were conducted in the field, and iii. Articles with available full text or abstract. In this study, all articles identified from the systematic search were added into Endnote X9 (Clarivate Analytics) and duplicate articles were removed. This study followed standard procedures for systematic reviews and reported results according to systematic reviews guidelines.
Results
Search results
In total, 637 documents were identified. Duplicated articles (351 articles) were removed and 52 full-text articles were reviewed. Finally, 13 studies that met the eligibility criteria were selected for this systematic review. The flow diagram of the study selection is shown in Figure 1. Articles were published between 1972 and 2017.  Eight articles were conducted in Esfahan province, while others were conducted in other provinces in Iran, including Yazd, Semnan, Kermanshah, Golestan, and Fars. The details of the results are shown in Table 1.


Figure 1: PRISMA flowchart describing the study design process.
Table 1: Characteristics of studies that focused on rodent control in Iran
No. Province Name of village Year of study Rodenticide Destroying of the rodent burrows radius (Meter) Main findings or suggestions Ref.
1 Esfahan  (Borkhar county) Colonabad
Juzdan
Sussart
Parvaneh
Jaladeran
Between June 1972 to September 1973 Mixture of Wheat with Zinc phosphide (2.5%) and DDT (75%) 300 M The number of rodent burrows and the incidence rate of ZCL significantly changed. 15
2 Esfahan  (Badrood) Abbasabad
Matinabad
Between December 1996 to January 1999 Mixture of Grain with Zinc phosphide (2.5%) 500 M Rodent burrows reduced by 87.4%, and the incidence rate of ZCL significantly changed. 16
3 Esfahan  (Natanz) Imamzadeh Agha Ali Abbas 1996-1998 Klerat® 2000 M The incidence rate of ZCL decreased.  17
4 Yazd (Ardakan) Ahmadabad Torkabad 1999-2000 Klerat® 2000 M The incidence rate of ZCL decreased.  18
5 Esfahan  (Badrood) Abbasabad Matinabad 1999 to 2002(May and October) Mixture of Grain with Zinc phosphide (2.5%) 500 M Rodent burrows changed over time in the intervention and control villages; moreover, the incidence rate of ZCL between the intervention and control villages significantly changed. 19
6 Semnan Villages of Damghan County 2005-2006 Mixture of Grain with Zinc phosphide 1000-2000 M The number of rodent burrows and the incidence rate of ZCL significantly changed. 20
7 Esfahan  (Natanz) Imamzadeh Agha Ali Abbas 2006-2009 Zinc phosphide 2000 M The number of people affected with ZCL decreased. 21
8 Esfahan Islamabad
Gishi
Vartoon
Parvaneh-Aliabadchi
2011 (April to November) Phostoxin and Zinc phosphide 500 M In the village, rodent burrows reduced by 32.68% and 58.14%, treated with phostoxin and Zinc phosphide, respectively. Moreover, the incidence rate of ZCL decreased to 19.23 and 11.40 in areas treated with phostoxin and Zinc phosphide, respectively. 3
9 Esfahan  (Esfahan) Mazraehshoor
Gishi
Vartoon
Parvaneh-Aliabadchi
January 2011 to January 2012 Mixture of Grain with Coumavec® and Zinc phosphide 500 M Rodent burrows reduced by 48.46% and 58.15% in intervention areas with Coumavec® and Zinc phosphide, respectively. Moreover, the incidence rate of ZCL significantly reduced in the treated areas. 6
10 Esfahan Timyart
Gishi
Vartoon
Parvaneh-Ali abdchi
2011 (April to November) Klerat® and Zinc phosphide 500 M Rodent burrows reduced by 62.8% and 58.15% in intervention areas with Klerat® and Zinc phosphide, respectively. Moreover, the incidence rate of ZCL significantly changed. 22
11 Kermanshah
(Qasr-e-Shirin)
Villages of Qasr-e-Shirin 2015-2016 Zinc phosphide (2.5%) 500 M The incidence rate of ZCL decreased. 23
12 Golestan 45 villages of Gonbad Kavous County 2016 (May, July and September) Mixture of Grain with Zinc phosphide (2.5%) 1000 M The number of rodent burrows and the incidence rate of ZCL significantly changed. 24
13 Fars
(Kharame)
Mehrabad
Moezabad
Sofla
2016 to 2017 Mixture of Wheat
with Fipronil
500 M The incidence of ZCL reduced by 4.89% in the studied villages. 25
Klerat®: Anticoagulant rodenticide containing 0.005% Brodifacoum.
Coumavec®:  A mixture of 0.5% coumatetralyl and 0.5% etofenprox.
Regional distributions of the studies
Based on the results of this review, rodent control operations have been concentrated in Central and North of Iran, and only one study was conducted in the West of Iran. Based on the results, rodents are more active as reservoirs of ZCL in Central and North of Iran. In total, 13 papers were found in the current review, eight of them were conducted in Esfahan province. The location of provinces in Iran where rodent control operation programs were implemented is illustrated in Figure 2.


Figure 2: Regional distributions of reported studies on rodenticides use in the reduction of ZCL in Iran.
Forms of rodenticide used
The findings indicated that 10 studies used zinc phosphide (2.5%) mixture with grain of wheat in rodent control programs in Iran. In three studies, Klerat® was used. Rodenticides such as Coumavec®, Fipronil, DDT (75%) and Phostoxin were also used in studies.
Figure 3 shows the rodenticide forms and the number of publications considered in the present systematic review.

Figure 3: Rodenticides used for each study in the current systematic review.
Rodenticides implementation method
Based on the reviewed articles, the method of applying rodenticides for each study was to destroy the rodent burrows at a distance of 1000 m from houses in the village, and then insert the poisoned baits to a depth of 10 cm in each burrow. A schematic of rodenticide implementation methods for each study in the current systematic review is illustrated in Figure 4.

Figure 4: Schematic of rodenticide implementation methods for each study in the current systematic review.
Discussion
Rodents are considered a public health pest, and their health impacts on humans and livestock are an immense issue in many countries. Rodenticides are widely used to manage urban rodents around the world, including in Iran. Based on the results of this study, zinc phosphide mixture with wheat grains and Klerat® have been known as the most common rodenticide in rodent control operations in Iran. In recent years, rodent control programs to control leishmaniasis in the field have been conducted by experts in five provinces of Iran, including Esfahan 3, 6, 22, Yazd 18, Semnan 20, Golestan 24, Kermanshah 23 and Fars 25. Based on the results of this review, rodent control operations have been focused on the Central and North of Iran, and only one study was conducted in the West of Iran. The results show that rodents are more active as reservoirs of ZCL in Central and North of Iran.
According to the results of rodent control operation studies published in Iran (13 papers), the incidence rate of ZCL significantly reduced following the implementation of rodenticides. Furthermore, most of the studies in different provinces of Iran reported that rodent burrows were reduced after rodenticides implementation. In most studies, rodent burrows were removed in a radius of 300 to 500 meters surrounding all communities. Therefore, after 48 hours, reopened holes were counted again in most studies.
In addition, 13 studies were conducted on rodent control programs in Iran for Phostoxin 1 tablet, zinc phosphide 12-15 gr, Klerat® 2 to 4 wax blocks, Coumavec® 12–15 gr, Fipronil 15gr, and DDT (75%). Based on the results, 0.5 gr of poisoned baits were inserted at a depth of 10 cm in each burrow in most studies, and only in one study, the poisoned baits were inserted at a depth of 30 cm in each burrow. There was no difference between the depths of poison baiting in the studies. Pesticides were mixed with grains of wheat, and poisoned baits were finally prepared.
The results of Seyedi-Rashti and Nadim (1974) showed that rodent control using zinc phosphide (2.5%) mixed with wheat and DDT (75%) was very effective 15. Based on the search results, this study is the first field study conducted in Iran. The results of Yaghoobi Ershadi et al. indicated that rodent control with zinc phosphide (2.5%) mixed with grain reduced the rodent burrows, and the incidence rate of ZCL significantly changed 16. Furthermore, Yaghoobi Ershadi et al. reported that rodent burrows changed over time in the intervention and control villages 19.
In another study, Veysi et al. reported that both rodenticides used, including Coumavec® and zinc phosphide mixed with grain, were adequate for reducing rodent holes in intervention areas and Coumavec® was less effective than zinc phosphide 6. Furthermore, t Veysi et al. in 2016 found that Klerat® was more effective than zinc phosphide in decreasing the rodent population 22. Coumavec® and Klerat® are chronic anticoagulant rodenticides that gradually affect rodents within 1–2 weeks. Previous studies did not recommend Coumavec® and Klerat® as alternatives for zinc phosphide to control the reservoir hosts of ZCL in the conventional situation. However, these rodenticides could be a suitable alternative to zinc phosphide under specific conditions such as behavior resistance or occurrence of bait shyness 6, 22.  
Similarly, Akhavan et al. stated that both rodenticides used in the study, including Phostoxin and zinc phosphide, were effective enough in controlling the rodent population 3. Kalteh et al. in Golestan province also reported a significant relationship between the implementation of rodent control operation and the incidence rate of ZCL in the studied villages 24. Saki et al. 25  found that the incidence rate of ZCL reduced in the studied villages.
Esfahan province is one of the essential foci of ZCL in Iran. Accordingly, , eight studies in this systematic review, including Seyedi-Rashti and Nadim 15, Yaghoobi Ershadi et al. 16, Nilforooshzadeh et al. 17, Yaghoobi Ershadi et al. 19, Nilforoushzadeh et al. 21, Veysi et al. 6, Veysi et al. 22 and Akhavan et al. 3 have focused on rodent control operations in this province.
In this systematic review, several studies such as Nilforooshzadeh et al. 17, Dehghani Tafti et al. 18, Azni et al. 20, Nilforoushzadeh et al. 21, and Ahmadi et al. 23 used a combined control program that included indoor residual spraying, rodent control, and improving the environment to reduce ZCL disease. These combined studies found that rodent control was a very effective method for reducing the incidence rate of ZCL in the studied villages. It appears that rodenticide can be used as a complementary method for reducing ZCL.
Conclusion
Rodent control programs are a promising and practical approach to reduce ZCL prevalence in Iran. For approximately five decades, the methods used for rodent control to reduce ZCL incidence in Iran have included chemical methods with rodenticides. The results of the present study demonstrated that rodent control programs to reduce ZCL incidence in Iran used rodenticides within 300 or 500 meters of houses. In studies conducted in Iran, 2.5% zinc phosphide mixed with a grain of wheat was the main rodenticide that was used. According to the results of the current study, the incidence rate of ZCL significantly reduced after rodenticide implementation. This systematic review provides a better understanding of rodent control program trends to control ZCL in Iran that have been conducted over the past 50 years and can serve as a reference for future field studies. However, more research is required to better understand the rodent control effect on reducing ZCL incidence.
Recommendations for future studies
Based on the information obtained from this systematic review, which encompassed rodent control research for reducing the incidence rate of ZCL in Iran over the past fifty years and collected information from 13 research articles, we would like to highlight some issues and make some recommendations that may be helpful for future studies on rodent control in the field. Various methods have been used to control rodent populations worldwide. Most research studies in Iran have focused on the use of toxic baits as a chemical method to reduce ZCL. It can be recommended that researchers focus on other methods. Some approaches for rodent control are recommended for future studies, as follows:
  • Using new rodenticides with new formulations, such as nano-rodenticides and encapsulated rodenticides.
  • Using another chemical method, such as fumigants and repellents.
  • Using physical methods such as traps and barriers.
  • Using an integrated pest management (IPM) strategy.
  • More studies should be conducted in other areas of Iran with ZCL foci to find a suitable practical method for rodent control in Iran.
The methods highlighted above can be expanded with specific experimental designs by researchers to further substantiate the utility of rodent control to reduce ZCL.
Acknowledgements
The authors would like to thank the Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences for supporting the current study.
Conflict of interest
The authors declare that there is no conflict of interest. 
Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.
Ethical considerations
This study was done without receiving ethical code.
Authors' contributions
All authors equally contributed to the preparation of this article.

This is an Open-Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt, and build upon this work for commercial use.

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Type of Study: Systematic Review | Subject: Environmental Health, Sciences, and Engineering
Received: 2023/11/3 | Accepted: 2024/01/20 | Published: 2024/03/13

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