Prevalence of soil-transmitted helminths infections among preschool and school-age children in Ethiopia: a systematic review and meta-analysis

Background There is a lack of comprehensive national data on prevalence, geographical distribution of different species, and temporal trends in soil-helminthiasis (STHs). Therefore, this study aimed to provide a summary and location of the available data on STHs infection among preschool and school-age children in Ethiopia. Methods The search was carried out in Medline via PubMed, Scopus, Science Direct, Web of Science, and Google Scholar on data published between 1997 to February 2020 for studies describing the rate of STHs infection among preschool and school-age in Ethiopian. We followed the Patient, Intervention, Comparison, and Outcome (PICO) approach to identify the studies. Meta-regression was performed to understand the trends and to summarize the prevalence using the “metaprop” command using STATA software version 14.0 Results A total of 29,311 of the 61,690 children examined during the period under review were infected with one or more species of intestinal parasites yielding an overall prevalence of 48% (95% CI: 43–53%). The overall pooled estimate of STHs was 33% (95% CI: 28–38%). The prevalence was 44% (95% CI: 31–58%) in SNNPR, 34% (95% CI: 28–41%) in Amhara region, 31% (95% CI: 19–43%) in Oromia region and 10% (95% CI: 7–12%) in Tigray region. Soil-transmitted helminths infection rate has been decreasing from 44% (95% CI: 30–57%) pre-Mass Drug Administration (MDA) era (1997–2012) to 30% (95% CI: 25–34%) post-MDA (2013–2020), although statistically not significant (p = 0.45). A lumbricoides was the predominant species with a prevalence of 17%. Conclusion Southern Nations Nationalities and Peoples Region, Amhara, and Oromia regions carry the highest-burden and are categorized to Moderate Risk Zones (MRZ) and therefore, requiring MDA once annually with Albendazole or Mebendazole. The prevalence of STHs decreased after MDA compared to before MDA, but the decline was not statistically significant. A. lumbricoides was the predominant species of STHs among preschool and school-age children in Ethiopia. The high prevalence of STHs observed in this review, underscores the need for better control and prevention strategies in Ethiopia. Supplementary Information The online version contains supplementary material available at 10.1186/s41256-022-00239-1.

Transmissions of the STHs are mainly by eggs or larvae that are passed with feces of an infected person or hatched in the soil after defecation. Adult worms residing in the gut of an infected person produce thousands of eggs every day, which may contaminate environments or foods that lack adequate sanitation [7]. Additionally, climatic conditions of tropical and sub-tropical countries are suitable for the survival of STH eggs and larvae hatching and embryonated in warm temperature and adequate moisture soil [8]. Consequently, the complication of STH may cause gut blood losses, malabsorption of nutrients, loss of appetites, and anemia due to loss of iron and other important protein [9]. For instance, the outcome of the infection on the children results in serious problems such as anemia, growth retardation, impaired cognitive developments, school absenteeism, and disability-adjusted life-years lost [10,11].
World Health Organization (WHO) has published comprehensive road map data in 2012 to combat Neglected tropical diseases (NTDs) by 2020. Mass Drug Administration (MDA) approach was also designed to undertake 75% coverage in all of the known endemic countries for STHs. The ideas of WHO was strengthened by the London declaration to control or eliminate other ten [10) NTDs in addition to the STHs [12,13]. Recently, following WHO strategic plan, Ethiopia has launched a nationwide MDA to control STHs, which targets 17 million children within the age range of 5-14 years old. The Ethiopian Ministry of Health and WHO started deworming in 2013, of which approximately 6.8 million and 7.8 million pre-school children (PSAC) and school-age children (SAC) were treated, respectively. Even before the deworming program, the ministry of health has undertaken some other measures to control poverty-related diseases including STHs among the population at risk, particularly SAC. For instance, the implementation of a health extension program focusing on creating awareness on latrine construction and utilization and keeping personal and environmental hygiene among the community is one priority program since 2003/2004. However, current individual reports indicated that the prevalence of STHs in Ethiopia is not declining. A large-scale study conducted in Amhara regional state showed that the prevalence of STHs was 36.4% [14]. Another study in Jimma town showed that the prevalence of STHs among SAC was 49.0% [15]. A similar study also reported that the prevalence of STHs was 47% in the rural community of Ethiopia [16]. Nevertheless, numerous fragmented studies have been carried out on assessing the prevalence of STHs among preschool children (PSAC) and SAC in Ethiopia, but comprehensive nationwide data on the prevalence, geographic distribution of different species, and time trends of STHs are lacking. Therefore, this study aimed to provide a summary of prevalence, geographical location, and time trends of STHs among preschool and SAC to measure the impact of the ongoing control and preventive measures in the country. In addition, such an effort might help the government and other concerned bodies to focus on specific areas of high prevalence for further preventive measures such as chemotherapy and improved sanitation practices.

Methods
We used and were guided by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) [17] guideline and checklist to carry out the current Systematic Reviews and Meta-analyses. The outcome of interest was the prevalence of STHs among PSAC and SAC in Ethiopia.

Search strategy
The search was carried out in Medline via PubMed, Scopus, Science Direct, Web of Science, and Google Scholar using searching terms such as "intestinal helminths'' , ''intestinal parasites'' , "soil-transmitted helminths", ''STHs'' , '' Strongyloides stercoralis '' , ''Ascaris lumbricoides'' , '' Trichuris trichiura'' , '' Hookworms'' , ''preschool-age'' , ''school-age'' , "Ethiopia". These key terms were combined using "AND" and "OR" Boolean operators. Medical Subject Headings (MeSH terms) were used to search relevant original articles in PubMed. Searching was carried out on articles published between 1997 to February 2020 and limited to English language and human studies. A manual search for additional relevant studies using references from retrieved articles and related systematic reviews was also performed to identify original articles we might have missed.
Endnote citation manager software version X 9 for Windows was utilized to collect and organize search outcomes (into relevant and irrelevant studies) and for the removal of duplicate articles. We followed the PICO approach to identify the relevant articles: Prevalence was calculated as the number of subjects positive for STHs in the study divided by the total number of participants in a study multiplied by 100.

Inclusion and exclusion criteria
We included observational studies conducted between 1997 to February 2020 which documented the baseline prevalence or incidence of STHs and studies published in the English language targeting both PSAC (< 5 years) and SAC (≥ 5 years). We excluded case reports, case series, studies that compared the sensitivity and specificity of different methods for diagnosis of STHs, and studies not reported either prevalence or incidence as an outcome of interest. This is due to those articles and/or reports will not adequately address the review objective. The current review didn't include unpublished studies or grey literature.

Data abstraction and quality assessment
Following preliminary assessment and downloading of the abstracts by two authors, they were assessed for agreement with the inclusion criteria. Irrelevant articles (articles that were out of the scope of the study) were excluded after assessment of the abstracts unless it was unclear to classify articles into irrelevant based on abstracts, where we downloaded the full text for further clarity. Once articles were deemed to be relevant, the full text of the articles was downloaded for further detailed review. We extracted information on the name of the first author and year of publication, study design, gender, region of study, laboratory method identification of the parasites, total sample size, the number of positives for intestinal parasites in general, number of positive for STHs in particular, and quality score for quality assessment. The Grading of Recommendation Assessment, development, and Evaluation (GRADE) approach was used to assess the overall quality of evidence [18]. Studies were given one point each if they had probability sampling, larger sample sizes of more than 200, and repeated detection, and up to four points could be assigned to each study. We regarded publications with a total score of 3-4 points to be of high quality, whereas 2 points represented moderate quality and scores of 0-1 represented low quality.

Statistical analysis
We used forest plots to estimate pooled effect size and effect of each study with their confidence interval (CI) to provide a visual summary of the data. A randomeffects model was used in this meta-analysis because of anticipated heterogeneity. Statistical heterogeneity among studies was expressed as the Cochrane's Q test and I 2 , where a p < 0.05 and I 2 values of 0, 25, 50, and 75% were considered as no, low, moderate, and high heterogeneities, respectively. Because we expected geographical variation and socio-economic contexts might differ radically across these studies, subgroup analysis based on the geography of the region, age children included, and year of publication. In addition to visual inspection for symmetry of the plot, we also used Begg's Funnel plot and Egger's regression test for quantitative evaluation of the possibility of publication bias. Meta-regression analysis was employed to identify the source of heterogeneity using regional states, age of children, publication years, and study design as covariates. All reported p values were 2-sided and were statistically significant if p < 0.05.

Literature searches and selection
Our initial search of electronic databases such as Medline via PubMed, Scopus, Science Direct, Web of Sciences, and Google scholar yielded 953 articles and 3 articles manually from which 213 records remained after removing duplications. Upon screening the articles, 123 articles were further excluded; 112 were irrelevant because they were not specifically about PSACor SAC, 6 studies were about sensitivity and specificity of diagnosis of STHs, and 5 articles were not about humans. Upon further assessment for eligibility, 2 studies were excluded being review articles. Finally, 88 [6,14,16, published studies between 1997 and February 2020 fulfilling the inclusion criteria were included in the final analyses (Fig. 1). The sample size of the included studies ranged from 100 [20] to 15,455 [14]. A total of 61,690 children with age of < 5 years (n = 5577) and ≥ 5 years (n = 55,731) or mix of both (n = 382) were recruited in the studies. Fifty-two percent (52%) of the study participants were male. The majority (83) of the studies were cross-sectional. Seventy-three studies were about STHs in SAC, thirteen were about preschool-age and the rest were studies that involved both PSAC and SAC. Thirty-five and twenty-four studies used Kato-Katz or in combination with other tools and formalin-ether concentration plus direct microscopic method for screening stools, respectively. Formalin-ether concentration techniques in 19 studies, direct wet mount method in 5 studies, McMaster in 4 studies, and Harada Mori (Test tube culture) technique in one study utilized as screening of stools. According to our quality assessment criteria, 43 publications were of high quality with a score of 3; 11 had a score of 2 indicating moderate quality; and the remaining 34 were of low quality with a score of zero or one ( Table 1).

The overall prevalence estimate of soil-transmitted helminths (STHs) and heterogeneity
Soil-transmitted helminths detected in the studies were Ascaris lumbricoides, Hookworms, Trichuris trichiura, and Strongyloides stercoralis. A total of 19, 678 of the 61,690 children examined during the period under review were infected with one or more species of STHs yielding an overall prevalence of 33% (95% CI: 28-38%) with substantial heterogeneity (χ 2 = 30,360.02, p < 0.001; I 2 = 99.71%) (Fig. 3). The asymmetry of funnel plot visual inspection (Fig. 4) showed that the presence of publication bias which was statistically confirmed by Egger's test (β = 16.7, [95% CI: 10.7-22.5]), p < 0.001 and Begg's test p < 0.001.    We did meta-regression analyses to search for the sources of heterogeneity. A univariate meta-regression between the prevalence of STHs and the age of children showed a statistically significant correlation (p = 0.003, Fig. 5). However, year of publications, (p = 0.076), regional states (p = 0.70) and study design (p = 0.23) did not show a statistically significant correlation as shown in Table 2.

Regional distribution of eligible studies and risk zones (RZs) for STHs infections
The highest numbers of studies were reported from Amhara 36 (40.90%) and SNNPR 22(25%). These were followed by the Oromia region 20 (22.7%), Tigray 8 (9.1%), Benishangul-Gumuz region, and Addis Ababa city each with one (1.1%) study. None of the regions is classified as High-Risk Zone (HRZ) according to the world health organization (WHO) risks classification. SNNPR, Amhara, and Oromia regions recorded STH prevalence of 44%, 34%, 31%, respectively and are classified as moderate-risk zones (MRZs) while, the rest of the regions and cities recorded prevalence estimates ranging between 1 and 10% and are classified as Low-Risk Zones (LRZs).

Discussion
The purpose of the current systematic review and metaanalysis of STHs infections data analysis among Ethiopian children was to measure the impact of the ongoing control and preventive measures in the country and support the efforts undertaken to control and eliminate neglected tropical diseases (NTDs) by nurturing or supplementing useful national epidemiological data. Such studies have the potential to guide concerned bodies to focus their efforts in highly endemic areas. Although several studies have been published from different regions of Ethiopia on STHs with the earliest scientific literature dating back 1990s, the data on STHs infections remains unorganized and scattered. Therefore, organizing and locating information has the potential to inform and develop a comprehensive approach to control STH infections and target highly endemic areas with greater urgency.
The overall pooled estimate of STHs (33%) observed in the present review is in line with the study from south America 27.1% [118], but higher than the study done in Iran (9.48%) [119] and Côte d'Ivoire (19.1%) [120]. The prevalence is lower than studies from Nigeria (54.8%) and reports from other Sub-Sharan African countries (52.4 and 65.8%) [121]. The variation between the findings might be attributed to differences in sensitivity and specificity of diagnostic methodology, environmental factors such as soil moisture, humidity, temperature, and level of participants' hygiene and sanitation. In addition, our review included more recent surveys that the ongoing MDA and Sustainable water, sanitation, and hygiene (WASH) programs decreased the prevalence of STHs in Ethiopian children unlike the systematic review from Nigeria which included old studies from the year 1985 [121].
Subgroup analysis of the current review also showed that STHs are more common in SNNPR, Amhara, and Oromia regions, although variation among the regional states was not statistically significant (p = 0.70). The majority of these infections are related to the low standard of living, poor socioeconomic status, poor personal hygiene, and poor environmental sanitation. The higher  prevalence of STHs infection among children in SNNPR, Amhara and Oromia regions might be also related to the high rainfall, forest, and low temperature which favors the survival and transmission of the helminths in these regions. The lowest prevalence in Addis Ababa, the capital city of Ethiopia, might be due to an advanced lifestyle, good personal hygiene, and good quality of life. Our review suggests that the risk of STH infections has decreased from 44 to 30% in studies conducted between 1997-2012 and 2013-2020 respectively, although the decline is not statistically significant (p = 0.45). Prevalence might have declined in some parts due to improvement in living conditions globally and expansion of major deworming efforts, including in Ethiopia. Nevertheless, the increase in population growth in Ethiopia is tremendous and therefore, might have increased the numbers infected and resulted in a slight decline in rate. It is also suggested that the widespread use of monotherapy of antihelminthic for deworming purposes might have facilitated the development of drug resistance and hence, decreased the rate of decline STHs in general and hookworms in particular [122,123].
If environmental and behavioral conditions are not changed at the same time that the chemotherapy program is being implemented, the prevalence will tend to return to original pretreatment levels through reinfection and therefore, need a holistic approach [3,[123][124][125][126][127][128]. According to WHO risk categorization, our finding (33%) indicates that MRZ of STHs requires MDA once annually, specifically in SNNPR, Amhara, and Oromia regions.
Concerning the species of STH, A. lumbricoides was the predominant species with a prevalence of 17% indicating that about one in six of Ethiopian children is living with Ascariasis. The current prevalence of the parasite is higher than the findings from other countries such as Iran (0.75%) and Srilanka (2.8%) which indicated that indoor and outdoor biotic contamination of the living environment arising partly from improper disposal of human waste, and partly from the integration of the lives of humans and animals of Ethiopian community might account for the still-high rate of the infection in the country. The finding of the current review (17%) is in line with findings from South America (15.6%), studies conducted in the Amhara region, Ethiopia (16.8%), and the overall burden in Sub-Saharan African countries (15%) [129]. However, it was lower than the results from Nigeria (44.6%), Rwanda (38.6%), Uganda (43.5%) [130], Kenya (24.3%) [131], and previous estimates in Ethiopia (37%). The observed differences might be due to variation in some factors putting the population at risk of acquiring STHs such as geographical variations, the lifestyle of the community, soil humidity, and exposure to contaminated environments.
In the current review, the prevalence of A. lumbricoides significantly decreased from 25% in 1997-2012 to 14% in 2013-2020 (p = 0.006). There was a 49% decline in the prevalence of A. lumbricoides observed before the implementation of the MDA program in school children compared to post-MDA. This risk reduction might be related to improved sanitation, access to better water supply, improved personnel hygiene, or the higher efficacy of the available treatments against A lumbricoides [122]. In support of this, a local study conducted on the efficacy of albendazole and Mebendazole indicated that the drugs have 95% efficacy in decreasing the burden of the parasite in Ethiopia [132].
The pooled prevalence of 6% observed for T. trichiura was higher than the 1.9% and 3.4% reported from Uganda [119] and Rwanda [121], respectively. The present finding is, however, lower than the reports of the disease burden of Sub-Saharan Africa (13%) [106], Nigeria (18.2%) [110], and Cameroon (15.6%) [118]. This might be due to the geographical variations, the lifestyle of the community, soil humidity, and exposure to contaminated environments. Meta-regression analysis by year of publication revealed that the prevalence of T. trichiura decreased from 14% in 1997-2012 to 4% in 2013-2020 (p = 0.03). The reason behind the substantial decrease in the prevalence of T. trichiura in the country during the study period might be due to the synergistic effect of overall improvements in sanitation, personnel hygiene, and deworming programs.
The finding of the current review showed that the prevalence of hookworms was 12% indicating that the current finding is lower than other studies conducted in Nigeria (32.7%) [121] and Uganda (18.5%) [130]. However, it was higher than studies conducted in Kenya (0.4%) [131], Rwanda (1.8%) [133] and Cameroon (3.9%) [134]. In general, increments of prevalence in our data might be attributed to the re-infection rate, low coverage or unequal distribution of MDA in all regions of the country, level of poverty (walking bare of the foot), and lack of good quality of life. For instance, most Ethiopians are living in the rural area and engaged in agriculture. Engagement in agricultural pursuits remains a common denominator for adult human hookworm infection, which might serve as a reservoir for reinfection of children [128]. Hookworm did not show a significant trend of decrement in prevalence between 1997 and 2012 (13%) as compared to the years between 2013 and 2020. This is, in contrast, to a study conducted in Nepal where the prevalence of Hookworms significantly decreased between the 1990s and 2015 [135].
Eliminating STHs as a public health has to go beyond preventive chemotherapy for SAC, as other groups at risk also serve as a reservoir of infection (preschool children and pregnant women, and even adults), which might have resulted in a slight decline again. It is also suggested that the widespread monotherapy of antihelminthic for deworming purposes might have facilitated the development of drug resistance and hence, decreased the rate of decline STHs in general and Hookworms in particular [122,123]. The strengths of our review include a rigorous search of several databases and other sources to identify eligible studies on the large pediatric population infected by STHs and generate data for policymakers to strengthen or modify the already ongoing control and prevent measures on the place. We also estimated the geographical distribution and identified risk areas that should be prioritized for MDA and other control interventions, which complement global efforts towards the elimination of STHs and other parasitic infections by 2020. In addition, this work also highlighted the need for surveys in areas where data are not available such as the Somalia region, Afar region, Harari, Dire Dawa city, and Gambela regions or scanty (Addis Ababa city and Benishangul-Gumuz region). There are a few limitations of the present metaanalysis. First, It is prudent to interpret the results of this study as 34(38.6%) of the included studies were low quality based on our quality assessment criteria. Second, in almost all of the studies included in this review, single stool sample examinations were used despite multiple stool samples recommendation for standard diagnosis, and therefore, there is a possibility for underestimation of the prevalence. Almost all studies included the current analyses examined the stool specimens for many parasites at a time and the diagnostic performance of such an approach is not known compared to studies that examine solely for STHs, such a diagnostic approach might affect the detection rate and prevalence estimates of STHs infections. Third WHO has recommended the Kato-Katz method as the best and most reliable diagnostic tool with better efficacy, accuracy, and predictive value than other techniques in resource-poor settings [136]. However, only 39.8% of the studies reported the use of the Kato-Katz method or in combination with other methods. Morbidity due to STH infections is a result of worm burden (number of eggs per gram of feces), otherwise called infection intensity. The disease prevalence is commonly combined with the intensity of infection to assess the epidemiological situation for STH infections and to classify communities into transmission categories, which enables the determination of the appropriate strategies for treatment and control [137]. However, only a few studies (13 out of 88) reported the intensity of infection of speciesspecific STHs, and thus, difficult to reach on definitive conclusion about the intensity of infection of STH in Ethiopia children. Therefore, there is an urgent need for a large-scale study to assess the intensity of infection of STH in children using the sensitive diagnostic tool on a repeated stool sample. Finally, the review protocol has not registered ahead of actual meta-analysis, which could be a source of bias.

Conclusions
Despite efforts made to reduce, STHs infection is still highly prevalent across the Ethiopian region with some degree of variation. Southern, Amhara, and Oromia regional states carry the highest burden. We observed a decreased prevalence of STHs among Ethiopian children post-MDA compared to preMDA, but the decrease is not statistically significant. A. lumbricoides had the highest prevalence among STHs. A. lumbricoides and T. trichiura were the most prevalent species in the Southern region while hookworms recorded the highest prevalence in the Amhara region. With effort made by the country in eradicating STHs infections, none of the regions in the country is classified as HRZ according to WHO risk classification. Southern, Amhara, and Oromia regions carried the moderate burden and are classified as MRZs, and therefore annual MDA is recommended while, the rest of the regions and city are classified as low-risk zones LRZs. We hope that the results of this study will provide valuable information to policymakers, the National Health Bureau, and other interested bodies, in particular on the endemicity, national and regional distribution, and the prevalence of STHs species in Ethiopia. The high prevalence of STHs observed in this review, underscores the need for better control and prevention strategies in Ethiopia.