Helminth Parasites among Rodents in the Middle East Countries: A Systematic Review and Meta-Analysis

Simple Summary The review was conducted to establish an overview of rodent helminths in the Middle East as well as their public health importance. Following a systematic search, 65 field research were identified, studied, and analyzed. The overall prevalence of cestodes, nematodes, and trematodes were 24.88%, 32.71%, and 10.17%, respectively. The review detected 21 species of cestodes, 56 nematodes, and 23 trematodes, from which 22 have zoonotic importance. Capillaria hepatica, Hymenolepis diminuta, Hymenolepis nana, and Cysticercus fasciolaris were the most frequent and widespread zoonotic helminths. The review identified that there is an information gap on rodent helminths at the humans-animal interface level in this region. Therefore, the public health importance of rodent-borne helminth parasites is not fully recognized. Countrywide detailed studies on rodent helminths, along with the impact on public health, should be conducted in this region. Abstract Rodents can be a source of zoonotic helminths in the Middle East and also in other parts of the world. The current systematic review aimed to provide baseline data on rodent helminths to recognize the threats of helminth parasites on public health in the Middle East region. Following a systematic search on PubMed, Scopus, and Web of Science, a total of 65 research studies on rodent cestodes, nematodes, and trematodes, which were conducted in the countries of the Middle East, were analyzed. The study identified 44 rodent species from which Mus musculus, Rattus norvegicus, and Rattus rattus were most common (63%) and recognized as the primary rodent hosts for helminth infestation in this region. Cestodes were the most frequently reported (n = 50), followed by nematodes (49), and trematodes (14). The random effect meta-analysis showed that the pooled prevalence of cestode (57.66%, 95%CI: 34.63–80.70, l2% = 85.6, p < 0.001) was higher in Saudi Arabia, followed by nematode (56.24%, 95%CI: 11.40–101.1, l2% = 96.7, p < 0.001) in Turkey, and trematode (15.83%, 95%CI: 6.25–25.1, l2% = 98.5, p < 0.001) in Egypt. According to the overall prevalence estimates of individual studies, nematodes were higher (32.71%, 95%CI: 24.89–40.54, l2% = 98.6, p < 0.001) followed by cestodes (24.88%, 95%CI: 19.99–29.77, l2% = 94.9, p < 0.001) and trematodes (10.17%, 95%CI: 6.7–13.65, l2% = 98.3, p < 0.001) in the rodents of the Middle East countries. The review detected 22 species of helminths, which have zoonotic importance. The most frequent helminths were Capillaria hepatica, Hymenolepis diminuta, Hymenolepis nana, and Cysticercus fasciolaris. There was no report of rodent-helminths from Bahrain, Jordan, Lebanon, Oman, United Arab Emirates, and Yemen. Furthermore, there is an information gap on rodent helminths at the humans-animal interface level in Middle East countries. Through the One Health approach and countrywide detailed studies on rodent-related helminths along with their impact on public health, the rodent control program should be conducted in this region.


Introduction
Helminths are among the most diverse and geographically widespread groups of parasites that infect both humans and animals [1]. Although they are from different phyla or class (nematode, cestode, and trematode), the mode of transmission, infection, and pathogenesis, as well as host immune-responsiveness of these pathogens, follows a typical pattern. Approximately one-third of the world population is infected with one or more types of helminths. From amongst 300,000 species of helminths that typically infect vertebrates, 287 of them infect humans, from which 95% are either zoonoses or have evolved from animal parasites [2]. About 100 of the zoonotic helminths cause asymptomatic infection or mild symptoms in humans, while only a small percentage of them cause severe or even fatal infections [1]. In resource-poor countries, livestock is a source of food, production, income source, and deposit of wealth. Parasite infections in animals indirectly affect human health through financial hardship and malnutrition. Based on the burden of death, sickness, and treatment cost for both humans and animals for helminth infestation, the zoonotic parasites' socioeconomic burden was presented as high or low socioeconomic impact [3].
Rodents are significant sources of parasitic zoonosis in humans, serving as reservoirs and vectors of at least 70 zoonotic diseases, of which 16 are helminth parasites [4]. Consumption of uncooked/improperly cooked food contaminated with the infective larvae, eggs, or metacercariae is the primary source of humans infestation with helminth parasites [5,6]. When pilfering humans food, rodents pass stool or urine that contaminates said food, leading to transmission of zoonotic helminths from rodents to humans [7].
The Middle East is an intercontinental region with a total population of over 411 million [8] in 17 sovereign countries, including Bahrain, Cyprus, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Oman, Palestine, Qatar, Kingdom of Saudi Arabia (KSA), Syria, Turkey, United Arab Emirates (UAE), and Yemen. The majority of people in this region live in poverty [9], with the highest percentage being specific to Yemen, Syria, Egypt, Palestine, and Iraq [10,11]. Cultural diversity, weak economic policy, poor governance, rapid population growth, low educational structure, gender discrimination, underdeveloped infrastructure, and war and conflict have turned the region into a hot spot for many emerging and re-emerging diseases, including rodent-borne parasitic infections [9,12,13]. In the past, rodent-borne infections have led to multiple instances of a fatal epidemic, in part due to a lack of relevant information available on the subject, which makes it difficult to maintain public health sustainability [14,15].
Helminth infestations are mostly neglected diseases [16]. Therefore, the complete picture of zoonotic helminths is not well known in the Middle East area. Despite several studies being done on helminths in this region, no systematic review or meta-analysis was performed on rodent helminths, including zoonotic importance in the Middle East region. Our objective is to summarize baseline information on rodent helminths in this region using evidence-based records of the helminths detected in rodents in the Middle Eastern countries. The review also identifies the rodent helminths with public health importance in this region.

Materials and Methods
We followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines [17] to conduct the systematic review using a four-step approach: database search, evaluating relevant articles, data extraction, and summarizing. One author conducted the data search. Two authors were involved in critical evaluation and data extraction from the selected articles, while one author managed the compilation of said data. Afterward, two authors arranged the data and conducted the meta-analysis (Figure 1, Supplementary Table S1).

Search of Relevant Articles
The data search results were processed using EndNote X9 (clarivate analytics, Philadelphia, PA, USA), which was also used to identify and exclude duplicate studies. Then we proceeded to peruse through the titles and abstracts to find the relevant articles. However, articles that were ambiguous regarding their relevance by their title and abstract were subjected to full-text analysis. Only documents published in English were considered for the review .

Data Extraction and Summarizing
Evidence-based field reports give a clear picture of any pathogen's availability, diversity, and dynamics in a locality [83,84]. We considered only the field reports containing rodent helminths for data abstraction. The extracted data included several variables such as country and location of sampling, season, year of sampling, rodent information (rodent species, sex, total rodent count, and the number of infected), helminth species and type, and possible associating factors of rodent infestation with helminth (Supplementary Table S2). The zoonotic rodent-borne helminths in this region were identified from the list of rodent helminths from this review with the support of published articles.

Data Analysis
The aggregated data was transcribed and stored in a Microsoft Excel spreadsheet, and then the data was forwarded to STATA/IC-13.0 (Stata Corp, 4905 Lakeway Drive, College Station, TX 77845, USA) for statistical analysis. Crude prevalence estimation was performed by dividing the total number of helminth-positive rodents with the total number of rodents sampled and expressed as a percentage. The crude estimate of prevalence was used throughout, the 95% confidence interval (CI), and the p-value were calculated on different types of helminths among the countries. Study variations among the studies were evaluated using the Chi-square (χ 2 ) test on Cochran's Q statistics (with p-value) followed by I 2 statistics to determine the study's degree of heterogeneity. Standard Error (SE) was calculated using a standard formula for proportion calculation. A random-effect meta-analysis model was applied using the "mean" command specifying random due to the study's high degree of heterogeneity (I 2 > 75%). The output has been illustrated using a forest plot [85].

Rodent Cestodes in the Middle East Countries
Rodent cestodes information was available from all 11 Middle Eastern countries (Supplementary Table S3). A total of 21 rodent cestode species that belongs to 8 families have been reported in this review. Most of the cestodes were from Egypt and Iran (12 cestode species from each county). Out of 44 rodent species, Mus musculus, Rattus norvegicus, and Rattus rattus were frequently identified with the cestode infestation. Three species of cestodes have been frequently reported, viz: Hymenolepis diminuta (20 reports from 5 countries), Hymenolepis nana (30,9), and Cysticercus fasciolaris (23,4). Figure 3 shows the prevalence estimates from individual studies on cestodes in rodents of the Middle East countries, which ranged from 7. 69

Rodent Nematodes in the Middle East Countries
Rodent nematodes were studied in 8 countries in the Middle East, namely Cyprus, Egypt, Iran, Iraq, Israel, Kuwait, Palestine, and Turkey (Supplementary Table S3). Nematodes from 23 families represented the 56 nematode species in this region. Most of the rodent nematodes were reported from Egypt (n = 24) and Iran (n = 31) and the rodent species such as Mus musculus, Rattus norvegicus, Rattus rattus, Meriones persicus, Acomys dimidiatus, and Tatera indica. However, the nematodes, Aspiculuris tetraptera, Capillaria hepatica, Syphacia obvelata, Streptopharagus kuntzi, and Trichuris muris were most frequently reported and widely distributed. These nematodes were reported from three or more countries in the Middle East. Figure 4 shows the prevalence estimates from individual studies on nematodes in rodents of the Middle East countries, which ranged from 0. 16

Rodent Trematodes in the Middle East Countries
The reviewed studies reported rodent trematodes in Egypt, Iran, Israel, and Saudi Arabia (Supplementary Table S3). At least 23 trematode species from 11 families of trematodes were reported in the Middle Eastern rodents. Reports from Egypt (n = 21) were more descriptive of these trematodes. Moreover, Fasciola sp. was detected in Saudi Arabia, Scaphiostomum sp. in Israel, and Notocotylus neyrai and Plagiorchis muris were identified in Iran. The review found Arvicanthus niloticus, Rattus norvegicus, and Rattus rattus are three rodent species important for trematode infestation. Figure 5

Zoonotic Importance of the Rodent Helminths in the Middle East Countries
Out of the 100 species of rodent helminths detected in this review, 22 species have zoonotic importance; 7 cestodes, 6 nematodes, and 9 trematodes. The zoonotic helminths, their hosts, and possible human infection sources have been illustrated in Table 2.

Discussion
This study reviewed the literature published in English on helminths-infested rodents in the Middle East region. The majority of the studies (47 of 65) were from Iran and Egypt, most likely due to their long history of rodent-borne zoonotic disease (like murine typhus, plague, tularemia) epidemics, which resulted in millions of death [4,[91][92][93][94]. Thus, this topic became a central focus of public health research in these countries. The present review found three commensal rodent species: Mus musculus, Rattus norvegicus, and Rattus rattus to be more common and carrying most of the zoonotic helminths within this region. Previous literature described that these species occupy different habitats with higher population density than the other species and pose considerable risk to public health [4]. Although rodent cestodes were most frequently reported (n = 50) helminth in this review, the meta-analysis detected the overall rodent nematode prevalence was highest (32.7%) compared to cestodes (24.88%) and trematodes (10.17%) prevalence. Out of the 22 zoonotic helminths detected in this review, Capillaria hepatica, H. diminuta, H. nana, and C. fasciolaris have been found as widespread distribution. Furthermore, some non-zoonotic helminths such as Aspiculuris tetraptera, Syphacia obvelata, Streptopharagus kuntzi, and Trichuris muris were reported from three or more countries in this region.
Rodents have several beneficiary activities in ecology, such as soil aeration and water absorption ability, biotic recovery, and insect control [4,95]. In this regard, the presence of healthy rodents is essential for ecology [96]. Helminths infestation in rodents affects their own health and can subsequently alter the rodent-environment ecology to a considerable degree. Moreover, rodent helminths are important for humans, livestock, and pet animal health. Hymenolepiais is a major zoonotic rodent cestode [6]. Fascioliasis is hazardous for livestock health as well as for humans [6,97]. The definite host of Taenia taeniaeformis is the cat, where a stage of this cestode lifecycle (the cystic form, Cysticercus fasciolaris) is completed in rodents. An increase of Cysticercus fasciolaris in rodents can increase the health risk of cats [98]. Thus, rodent helminths have an impact on the ecology as well as humans and animal health.
There is an information gap on rodent-borne zoonotic helminths in the Middle East countries. Some zoonotic cases of helminths infestation were reported in rodents by some countries in the Middle East, but none involved humans who might have been infected with the same helminths. Humans hymenolepiasis were reported in Bahrain [101], Cyprus [102], Jordan [103], Oman [104], Palestine [105], Qatar [106], and Yemen [107]. The Hymenolepis nana is a common zoonotic helminth transmitted from rodents to humans and the prevalence ranged from 0.15% to 12.2% in some Middle East countries with prevalence of specific countries such as Jordan (1.8%) [103], Oman (5.9%) [104], Palestine (1.0%) [105], Qatar (0.15%) [106], and Yemen (12.2%) [107]. Egg of Hymenolepis diminuta was detected from soil samples of school playgrounds of Jordan [108]. There is no report of rodent hymenolepiasis within these countries. Echinococcus spp. is a major helminth for human health, which was detected in rodents of Egypt, Iran, and Turkey. Human cases of alveolar hydatid cysts were reported from Iran, Kuwait, Saudi Arabia, and Turkey [109,110].
Based on the meta-analysis, the overall prevalence of rodent trematodes was less than that of nematodes and cestodes in the Middle East, which had received more emphasis in other similar reports [110,127]. Efficient management of water resources are important factor for prevalence of trematode prevalence [139,140]. The presence of deserts means shortage of surface water in some of the countries of Arabian Peninsula such as Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and United Arab Emirates [141], which may be the cause of shortage of aquatic intermediate hosts of trematodes in these countries. Therefore, rodent trematodes are less reported in these countries. More research should be conducted to find rodent-borne trematodes in the countries of this region.
The reviewed articles in the current study described some of the factors that can influence the population of rodent-borne helminths within the Middle East, necessitating a need to develop a plan of action to control rodent helminths. The abundance of rodent-borne helminths depends on the host organism's prevalence and its distribution [29,44]. An increase in the rodent population may increase the risk of humans getting infected by rodent parasites [142]. Rodents who inhabit animal farms have easy access to animal feed, and thus, they can be considered a potential vector and reservoir of animal and zoonotic diseases where animals serve as hosts [26]. Hymenolepis diminuta in the rodent are linked with some insects as intermediate hosts, such as Xenopsylla astia, which has a clear seasonal pattern. In Qatar, a research found that rodents are more infested with Hymenolepis diminuta in summer due to the X. astia abundance [24]. Several studies reported that the prevalence of rodent helminths is increased with rodent age [23,24,35,51]. Rodent helminths infestation can change with rodent host species [48]. The nematode, Syphacia obvelata, was reported to be most abundant in Mus musculus [64].
Rodent population control is a primary way to control rodent zoonotic diseases [143,144]. The other contributing factors, such as rodent species, seasons of the year, intermediate host, rodent control management in the residential areas, and animal farms, should also be considered on rodent related zoonoses control. As most of the rodent-related zoonotic helminths are linked to herbivores and carnivores [5,6,86,88], it is vital to manage dogs, cats, and livestock animals to avoid the spread of helminth infestation. Thus, One Health practice comes as a practical approach to control rodent-borne helminth prevalence [145]. "One Health is a collaborative, multisectoral, and transdisciplinary approach -working at the local, regional, national, and global levels-with the goal of achieving optimal health outcomes recognizing the interconnection between people, animals, plants, and their shared environment" [146]. One Health practice by linking veterinary, medical, ecology, entomology, parasitology, zoology fields, and local people are essential for rodent helminths prevention and control.

Conclusions
Rodent helminths in the Middle Eastern countries have been documented, which also highlighted rodent-borne zoonotic helminths. Rattus norvegicus, Rattus rattus, and Mus musculus were the most frequently reported rodents and infected with helminth parasites. Out of the 22 rodent-related zoonotic helminths, Capillaria hepatica, H. diminuta, H. nana, and C. fasciolaris were most frequent in this region. The current study illustrates that there is an information gap on the availability, diversity, and dynamics of rodent helminths and their interaction between humans and animals in the Middle East. Thus, the public health importance of rodent-borne helminth parasites is not fully recognized. However, rodent control should be the primary concentration by a One Health approach to control the spread of these helminths at the humans-animal-environmental interface in the countries of this region. We also suggest countrywide and detailed studies be conducted on rodent-borne helminths along with their impact on public health in this region.

Acknowledgments:
The authors acknowledge the Qatar National Library for providing some full-text articles and partially paying the publication fee.

Conflicts of Interest:
The authors declare no conflict of interest.