Trend of Soil-Transmitted Helminths in Ethiopian Children: A Systematic Review and Meta-Analysis (2000-2018)

Background Ethiopia is one of the tropical countries with a heavy burden of soil-transmitted helminths. As a result, the nation has been implementing mass drug administration, water, sanitation, and hygiene and health extension programs to control those parasites. Hence, updated data about the prevalence and trend of parasites over time has a pivotal role to assess the success of existing control programs. Methods Studies conducted between 2000 and 2018 were searched from PubMed, Google Scholar, and local journals for systematic reviews and meta-analysis following the PRISMA guideline and checklists. Eligible studies were selected based on preset inclusion and exclusion criteria. The quality of the included studies was assessed using the Newcastle-Ottawa Scale in meta-analysis. Heterogeneity between studies was assessed using the Cochran Q test and I2 test statistics based on the random effect model. Comprehensive meta-analysis (CMA 2.0) was used to calculate the pooled prevalence, and metaregression was run to assess the trend of parasite prevalence over time. Results Thirty-eight studies recruiting 16,266 participants were included in the review. The pooled prevalence of intestinal parasites was 52.0% (95% CI: 44.4-59.5). Amhara region was with the highest prevalence (60.3%; 95% CI: 50.1-69.6). Among soil-transmitted helminths, Ascaris lumbricoides (11.2%; 95% CI: 8.4-14.8) was with the highest pooled prevalence followed by hookworms (10.4%; 95% CI: 7.9-13.7) and Trichuris trichiura (3.6%; 95% CI: 2.4-5.4). Metaregression analysis revealed that all soil-transmitted helminths did not show a significantly decreasing trend over time (p > 0.05). Conclusion Despite various control efforts having been made, soil-transmitted helminths are of high distribution, and their prevalence is not significantly decreasing in Ethiopia. Hence, other control approaches like community-led sanitation should be integrated with mass drug administration to achieve the national goal of soil-transmitted helminth elimination by 2025.


Background
Intestinal parasitic infections (IPIs) are among the major public health problems worldwide. Globally, 3.5 billion people are infected, among which 450 million manifest illnesses because of the infection [1]. Poor sanitary conditions and conducive climate for the survival of parasites outside the host make the majority of intestinal parasites (IPs) abundant in the tropics [2]. Globally, Ascaris lumbricoides (A. lumbricoides), Trichuris trichiura (T. trichiura), and hookworms infect 819, 465, and 439 million people, respectively. They are grouped under soil-transmitted helminths (STHs) because their infective stages embryonate or develop in the soil [3].
In Ethiopia, 81 million people are at risk of STH infection. School-age children (SAC) account for nearly onethird (25.3 million) of the risk population [4]. Transmission of STHs is associated with personal hygiene and sanitation practices as well as access to safe water. However, the Ethiopian Demography and Health Survey report shows that 40% and 33% of households had no hand washing facilities and toilets at their home. Access to safe water for drinking was also poor in the rural community with only 57% coverage [5]. These conditions contribute to ease of transmission for IPs in general and STHs in particular [6].
Even if all population groups can be infected by STHs, SAC are the most commonly affected groups. This is because of their immature immune system and frequent exposure to infective sources (soil and water) as well as poor hygiene and sanitary practices [7,8]. Moreover, children are more vulnerable to serious complications such as prolonged diarrhea, malnutrition, anemia, bowel obstruction, and learning disabilities compared to adults [9]. Hence, the Federal Ministry of Health of Ethiopia has been taking strong measures targeted for the control of IPs among SAC. Implementation of the health extension program since 2003/4, which focuses on the preventive health packages, has brought tangible improvements in the health of the rural community. Creating awareness about latrine construction and utilization as well as keeping personal and environmental hygiene among the community has been one of the priority concerns of the program [10]. Implementation of biannual mass drug administration (MDA) with albendazole or mebendazole for the control of STH since 2015, primarily targeting SAC, has been the other important commitment of the ministry [11].
All these efforts are expected to reduce the burden and health impacts of STHs from time to time. Several survey studies have been conducted among SAC at different geographical settings of the country. However, there is no adequate data reporting the pooled prevalence and trend in magnitude of STHs over time. Hence, we conducted a systematic review and meta-analysis aimed at assessing the pooled prevalence and trend of STH infections among SAC in Ethiopia. The review provides evidence about the impact of ongoing control and prevention programs and to plan for the future. In this review, we did not include Strongyloides stercoralis because we need to focus on the main STHs which have been targeted for MDA-based intervention so that we can analyze the impact of MDA on their prevalence. Moreover, there have been controversies whether Strongyloides stercoralis fulfills the definition of STHs.

Setting.
We included studies conducted all over Ethiopia. Ethiopia is located in the horn of Africa at geographical coordinates of 8°N and 38°E [12]. The country is composed of nine regional states and two city administration councils. Altitude of the country ranges from high peaks of 4,620 meters above sea level to a low depression of 148 meters below sea level. More than half of the country lies above 1,500 meters [4,12]. The estimated population of the country for 2018 was 107.53 million where SAC of age 5-14 years account for 31.2% [4,13].

Eligibility Criteria.
School-or community-based studies conducted in Ethiopia between January 2000 and December 2018 targeting SAC (4-25 years old) and published in the English language were included in the present review. Studies reporting both intestinal protozoa and helminths or intestinal helminths alone were included since our primary targets were STHs.

2.
3. Information Sources and Search of Literature. Potential articles were searched in PubMed, Google Scholar, and local journals following the PRISMA guideline and checklists [14]. Search in PubMed was done using the MeSH terms "helminth OR intestinal helminth OR helminthiasis OR intestinal parasite OR parasite OR parasitosis OR intestinal parasitosis OR parasitic infection AND Ethiopia." A manual search was also conducted on all relevant references listed within the articles identified after an initial electronic search. The search was independently done by two reviewers to minimize bias and missing of studies.

Study
Selection. The study selection process is shown in Figure 1. Studies conducted in health facilities were excluded because we expect inflated data as only symptomatic children with parasitic illness participate in healthcare facility-  Journal of Parasitology Research based studies. Because our interest in this review was the SAC, the most susceptible group for IPI, studies targeting preschool children and adults alone were not considered. Surveys conducted before January 2000 and those reporting only intestinal protozoa were also excluded from the review.
Published surveys reporting at least the age group of study participants, location of data collection, and data collection period were included in this review ( Figure 1). The search was conducted by two authors separately, and there were differences in the inclusion of the three studies. After discussion, both authors agreed to include two and excluded one study.
2.5. Data Extraction. Two authors extracted data independently using a standard data collection form constructed in Excel. Information was collected about the total number of children that participated, total number of children with laboratory confirmed intestinal parasitosis, age group, year of 3 Journal of Parasitology Research study, location of sampling (study region), laboratory methods used for investigation of fecal specimens, groups of parasites detected (helminth only/helminth and protozoa), and total number of children infected with the big three STHs (A. lumbricoides, hookworms, and T. trichiura).
2.6. Statistical Analysis. Estimation of the pooled prevalence of IPIs and summary prevalence of each STH was calculated using CMA 2.0 software. Subgroup analysis was done by region of study and study period. The random effect model was used in the analysis because the study populations across selected studies vary, at least in terms of age group and level of risk of IPI. Heterogeneity between studies was checked with a forest plot, Cochran's Q test, and I 2 test. Significant heterogeneity was declared at I 2 > 50% and Q test (p < 0:10). Quality of study was checked with the Abdi, 2017              Journal of Parasitology Research [47][48][49][50][51][52] except 1 which was conducted at the community level [46]. Eleven and nine studies screened stools by formol ether concentration and Kato-Katz techniques, respectively, while seven studies performed both direct wet mount and formol ether concentrations (Table 1).

Discussion
The present systematic review and meta-analysis was designed to generate comprehensive data about the national  9 Journal of Parasitology Research prevalence of IPs in general and STHs in particular. Accordingly, studies assessing the prevalence of IPIs, conducted in different regions of Ethiopia, were gathered and analyzed to estimate the national pooled prevalence. The findings provide useful epidemiological data to aid in the control of STHs. The review generated information about the distribution of the big three STHs: A. lumbricoides, hookworm, and T. trichiura in Ethiopia which, in turn, helps to evaluate the success of existing control programs and to plan for the future. It also helps to implement targeted control activities. The overall pooled prevalence of IPs in the present review (52.0%) was similar to the 47.6% prevalence in Afghanistan [53] but higher than the prevalence in Iran (38%) [54], Syria (42.5%) [55], Turkey (31.8-37.2%) [1], and Egypt (27%) [56]. Variations in the distribution of IPs among different geographical settings as well as the type and level of control program implementation across countries might be responsible for these differences.
The pooled prevalence of hookworms in the present review (10.4%) was in line with review results from South America (11.9%) [57]. It was lower than the Ethiopian national estimate of 16% before 10 years [58] and a regionwide survey in the Amhara region (20.6%) [59] pronounced the impact of MDA and WASH activities since then. Subgroup analysis of the current review also shows the highest prevalence of IPs in the Amhara region. The prevalence was also lower than the pooled prevalence from Nigeria (23.0%) [54] and Rwanda (31.6%) [60]. The cumulative number of children included in the review from Nigeria was higher compared to the present review (34,518 vs. 16,266) [54]. Moreover, we have included more recent surveys that the ongoing MDA and WASH programs also impact the prevalence of hookworms unlike in reviews from Rwanda which included studies starting from the year 1940 [60].
Implementation of intervention programs mainly improved healthcare coverage and biannual MDA, and WASH has been thought to bring a decreasing trend of both morbidity and prevalence of STH infections over time. As a result, hookworms show a decreased prevalence between the years 2014 and 2020 (8.7%) compared to that of the years 2000-2013 (11.7%). However, the trend in decrement was not significant (p = 0:138). This is to the review results from Nepal where hookworm infections significantly decrease between the years 1990 and 2015 [61]. Interventions for STH transmission in Ethiopia primarily target SAC. However, in rural areas where fields are fertilized with night soil, STH species like hookworms may heavily infect adults who, in turn, serve as sources of infection for SAC [59]. Open defecation is common in rural communities of Ethiopia that reinfection of treated children also contributed to the nondecreasing trend of the parasite.
The pooled prevalence was higher than findings from nationwide surveys in Sri Lanka (1.2%) [62] and Cameroon (1.55%) [63]. In both countries, the authors used a single Kato-Katz smear, and there is also variation in geographical distribution as well as adoption and level of implementation of control programs across countries.
The pooled prevalence of A. lumbricoides in the present review (11.2%) was in line with findings from Cameroon (11.48%) [63]. However, it was lower than results from Nigeria (44.6%) [64], Rwanda (38.6%) [60], South America (15.6%) [57], the Amhara region of Ethiopia (16.8%) [59], and a previous estimate in Ethiopia which was 37% [58]. Local studies about mebendazole and albendazole efficacy show that both drugs have more than 95% efficacy against A. lumbricoides and that the ongoing MDA has substantially decreased the burden of the parasite in Ethiopia [65]. However, the trend of A. lumbricoides was not uniformly decreasing between the years 2000 and 2020 (p = 0:610) with the possible reason of poor WASH implementation in the country [5]. The pooled prevalence of A. lumbricoides in the present review was higher than the review result of 0.75% from Iran [54] and 2.8% from Sri Lanka [62].
The pooled prevalence of T. trichiura in the present review (3.6%) was in line with reviews from the Amhara region (3.8%) [59] and Sri Lanka which was 4% [62]. On the other hand, it was lower than review results from South America (12.5%) [57], Nigeria (31.9%) [64], Cameroon (18.22%) [63], Rwanda (27%) [60], and previous estimates in Ethiopia (30%) [58]. The pooled prevalence of T. trichiura in the present review was higher than the review result of 0.12% from Iran [54]. Metaregression analysis by year of study showed that T. trichiura has almost constant prevalence between the years 2000 and 2020 in Ethiopia. Both albendazole and mebendazole, drugs used for MDA, have poor efficacy against T. trichiura contributing to the nondecreasing trend of parasite prevalence [65].

Strength and Limitations.
The strength of the present review is that it included a large number of studies and has identified the pooled prevalence of the big three STHs which are targeted for control in Ethiopia. As a limitation, the studies included in the present review were conducted in only five regions and we could not get studies from other regions. The primary targets of this review were SAC; however, many studies have included adolescents. Considering a very small proportion of participants are above the age limit of SAC and with the concern not to miss potential findings, we included studies which recruited participants of age 4-25 years old. There was also variation in laboratory techniques used across the reviewed studies. The pooled total IP prevalence in the present study might not show the exact figure in the country because studies not reporting STH were excluded as STHs were the focus of the present review [66].

Conclusion
The prevalence of IPs in Ethiopia is unacceptably high infecting more than half of the population. This is against the national goal. The federal Ministry of Health has set a goal to eliminate the three STHs (ascariasis, hookworm infection, and trichuriasis) as public health problems by 2025. Despite various control efforts having been made, STHs are with high distribution and their prevalence is not significantly decreasing in Ethiopia. Hence, the integration of the existing control activities (MDA and WASH) accompanied with continuous efforts to create awareness and engagement among the community should be promoted to achieve the national goal of STH elimination by 2025. Alternative treatment options like combination therapy of albendazole/mebendazole with ivermectin should be considered for trichuriasis.

Data Availability
The original data for this study is available from the corresponding author.