Epidemiology of intestinal parasitic infections in Ethiopian children: A systematic review and meta-analysis

Background : Numerous studies have been carried out on assessing the prevalence of intestinal parasites infections (IPIs) among preschool and school-age children in Ethiopia, but there is lack of study systematically gathered and analyzedinformation for policymakers. Therefore, the aim of this systematic review and meta-analysis was to provide a summary on prevalence, geographical distribution and trends of IPIs among preschool and school-age childrenin Ethiopia. Methods :The search were carried out in Medline via PubMed, Scopus, Science Direct, Web of Science, and Google Scholar from 1996to July2019 for studies describing prevalence of IPIs among preschooland school-age children. We conducted meta-regression to understand the trends and the source of heterogeneity and pooled the prevalence using ‘metaprop’ command using STATA software version 14. Results : Eighty-three(83) studies examining 56,786 fecal specimens were included. The prevalence of IPIs was 48 %( 95%CI: 42% to 53%) and showedsignicantly decreasing trends 17% (95% CI: 2.5% to 32%) for each consecutive 6 years) and was similar in males and females. The pooled prevalence in years 1997–2002, 2003–2008, 2009–2014 and >2014 was 71% (95% CI: 57% to 86%), 42% (95% CI: 27% to 56%), 48% (95% CI: 40% to 56%) and 42% (95% CI: 34% to 49%), respectively. Poly-parasitism was observed in 16% (95% CI: 13% to 19 %,) of the cases. Conclusion: Intestinal parasite infections are highly prevalent among preschool and school-age children and well distributed across the regional states of Ethiopia. Southern and Amhara regional states carry the highest burden.We observed signicant decreasing trends in prevalence of IPIs among preschool and school-age Ethiopian children over the last two decades.Therefore, this study is important to locate the geographical distribution and identied high risk areas that should be prioritized further complement of IPIs by 2020


Participants, inclusion and exclusion criteria
Two authors independently(LCH&DE) assessed the inclusion criteria and disagreement was solved by discussion with the third author (ZM). We included the studies if they met the following criteria: the study design was an observational study (prospective cohort, case-control, retrospective cohort, or cross-sectional) or controlled clinical trial which documented the baseline prevalence or incidence of IPIs. We included all studies reported the rateor proportion of IPIs in preschool and/or school-age children or both. We excluded studies reporting case reports, case series, studies that compared the sensitivity and speci city of different methods used for diagnosis of intestinal parasites and studies not reported either prevalence or incidence of IPIs as outcome of interest. The terms preschool and school-age children were de ned according to the original studies. Accordingly, preschool-age children were de ned aschildren of age below 5 years while,school-agechildren were children of age 5 and above. Poly-parasitism was de ned as concurrent infection with different species of intestinal parasites either helminths or protozoa.

Data extraction and Quality assessment
The two authors (LCH and DE) de ned protocol for data extraction and assessed them independently for eligibility and disagreements were resolved by discussion with the third author (ZM). We extracted information on name of the rst author and year of publication, study design, population studied ( preschool age children, school age children or both), gender, region & sites of study, Method (s) for identi cation of the parasites, total sample size and the number of the positives (percentage). The Grading of Recommendation Assessment, development and Evaluation (GRADE) approach was used to assess the overall quality of evidence [26].Accordingly, studies were given one point each if theyhad probability sampling, larger sample sizes of more than 200, and repeated detection and up to four points could be assignedto each study.Publications with a total score of 3-4 points were considered as 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 con dence interval (CI) to provide a visual summary of the data. A random-effects model was used in this meta-analysis because of anticipated heterogeneity. All reported P values were 2-sided and were statistical signi cant if P < 0.05. Statistical heterogeneity among studies was expressed as the P value (Cochran's Q statistic), where a P < 0.05 and I 2 ≤ of 25-50% were considered as low heterogeneity and I 2 >50% indicated substantial heterogeneity.We also used Begg's Funnel plot and Egger's regression test for evaluating the possibility of publication bias. A potential source of heterogeneity was investigated by subgroup andmeta-regression analysis.The factors included were geographical regions and cities of Ethiopia, age of children (preschool vs. school-age children), and years of publication (1997-2002, 2003-2008, 2009-2014 and > 2014). We conducted meta-analysis using 'metaprop' commandusing STATA software, version 14, STATA Corp,College Station, TX.

Literature searches and selection
We identi ed systematically 1,198 publications, of which 83 were eligible for inclusion in the nal analyses. The details of our search strategy were depicted in Figure 1. Our initial search of electronic databases such as Medline via PubMed, Scopus, Science direct, Web of Sciences and Google scholar yielded 1195 articles and 3 articles manually from which 186 records remained after removing 1012 duplications. Up on screening the articles, 99 articles were further excluded; 90 were irrelevant because they were not speci cally about preschool or school-age children, 6 studies were about sensitivity and specify of diagnosis of IPIs, 3 articles were review articles. Up on further access to the full texts of 87 articles, 4 were excluded for the following reasons; 2 were meta-analyses and 2 articles lacked outcome of interest. Finally, 83 published between 1997 and 2019 ful lling the inclusion criteria were included in the analyses.  [93][94][95][96][97][98][99][100][101][102][103][104][105][106][107]. Most of the studies were reported from Amhara regional 33(40%) followed by Oromia region 21(25%). The rests were reported from South region 18(22%), Tigray region 9(11%), Benishangul-Gumuz region 1(1%) and Addis Ababa city 1(1%). With regard to the study design, majority of the studies were cross sectional in design (79 studies), 2 were controlled clinical trials, 2 were prospective follow up cohort studies and 1 was case-control.Sixty six studies were about IPIs in school-age children, 13 were in preschool-age children (under-ve) and 4 were studies involved both preschool and school-age children.According to our quality assessment criteria, 34 publications were of high quality with a score of 3, 12 had a score of 2 indicating moderate quality and the remaining 37 were of low quality with a score of zero or one [Table1].Prevalence estimate and heterogeneity analysis A total of 27,354 of the 56,786 children examined during the period under review were infected with one or more species of intestinal parasites yielding an overall prevalence of (n = 27,354) 48 %( 95%CI: 42% to 53%) with substantial heterogeneity (I 2 = 99.50%, regression coe cient: -0.23, 95% CI: -0.38 to -0.09, p= 0.002, Fig. 2). A range of parasites were detected in the studies includingAscaris lumbricoides, Hookworm, Trichuris trichuria, Strongyloides stercoralis, Enterobius vermicularis, Schistosoma mansoni, Hymenolepsis nana, Taenia species, Giardia lamblia/intestinalis/duodenalis, Entamoeba histolytica/dispar and Cryptosporidium species. Subgroup analysis showed that the prevalence of IPIs was 56% (95%CI : 39% to 73%) in Southern region, 51%(95%CI : 43% to 58%) in Amhara region, 40% (95%CI : 31% to 50%) in Oromia region, and 41%(95%CI: 28% to 54%) in Tigray region as shown in Fig. 3 and 4. The age related prevalence was 52% (95%CI: 46% to 58 %,) in school-age children and 30% (95%CI: 18% to 34%) preschool-age children (p= 0.002) as shown in Fig. 5.

Discussion
The pooled prevalence of IPIs in preschool and school-age Ethiopian children was 48 %( 95%CI: 42 to 53%). The prevalence is higher in Southern (56%) and Amhara regions (51%).We observed a signi cant decrease in the prevalence of IPIs among children in Ethiopia over the last two decades (22 years). The burden of infection was higher among school-age children compared to preschool-age children (52% vs.30%, p = 0.002), however, it was similar in males and females as well as in urban and rural inhabitants. Poly-parasitism was observed in 16% of preschool and school-age children while, single infection was documented in 36% of the children participated in the study.
The overall pooled prevalence estimate (48%) observed in the present systematic review and meta-analysis is similar to the study from Nigeria (54.8%) [109], Rwanda (50.5%) [110], Afghanistan(47.6% ) [111] ,Syria (42.5%) [112] and in Palestine (40.5%) [113]. However, the nding of this systematic review and meta-analysis is higher than that of Cameron(24.1%) [114], Rwanda (25.4%) [115], Iran (38%)[116], Turkey(31.7%-37.2%) [117] and Egypt (26.5%) [118]. The difference might be attributed to socio-economic status, poor hygiene and sanitary facilities, weather, climate and environmental factors. For example, a study in Ethiopia showed that Ascaris lumbricoidesinfections were more common in children living in households with lower incomes (prevalence ratio = 6.68, 95% CI = 1.01-44.34) and that Giardia lamblia infections were more common in children living in households that used an unprotected water source (prevalence ratio = 1.95, 95% CI = 0.96-3.99) [32]. In addition, most Ethiopian communities have the habit of consuming uncooked meat, which mightincrease the risk of exposure to human helminths. Many of Ethiopianpopulation where the studies conducted involved in irrigation activities for the cultivation of vegetables during the dry season. This irrigation canals create media for the reproduction of vector snails, which might be the cause of the appearance of endemicity of Trematodes infections in the area. It might also be attributed to the speci city and sensitivity of the diagnostic methods employed by the individual studies.
The meta-regression of prevalence of IPIs over time showedsigni cant decreasing trends in each 6-years block by 17% (95% CI: 2.5% to 32%) and this declined prevalence was probably due to socioeconomic development, improvement in sanitation and large-scale deworming programs. Many studies from around the world have reported a signi cant decreasing trend in the prevalence of overall IPIs in recent years ,such as the global burden of disease study [5], study from Burkina Faso [119], Nepal [120], Brazil [121] and other from 43 Sub-Saharan [122]. Despite many initiatives and efforts to introduce mass deworming program and improvement in water quality and sanitation, IPIs are still prevalentand the decrease in trend is less than that of other countries (Ethiopia 42% in 2016-2019 vs. Nepal 20. 4% in 211-2015 and Brazil 23.8% in 2010-2011).This might be possibly due to insu cient nancial supports in implementation of the strategies that have been known to reduce the infection such as access to safe water supply, personal hygiene and sanitation, deworming and public health awareness.. In addition, lack of political commitment, social and environmental factors might also contribute for the higher prevalence of IPIs in the country. Inadequate community involvement and ownership of control activities are also another possible reason.
The prevalence of IPIs in school-age children was (52%), which was signi cantly higher than in preschool-age children (30%). This is similar to the study by Jayarani 2014 [123] and Workneh 2014 [45], but opposite to the study by Daryani 2017[116]. School children carry the heaviest burden of the intestinal parasite associated morbidity due to their habits of playing or handling of contaminated soils, eating with soiled hands, unhygienic toilet practices, drinking and eating of contaminated water and food [22] compared to preschool-age children who usually cared by families. The current control efforts in Ethiopia usually target school-age children, but a signi cant proportion of preschool-agechildren (30% in this study) were also infected and can be source for the re-infection of treated schoolage children. Therefore, it worthy revising the national control program based on regional and national prevalence which included preschool children and other population at risk.
In the present study, the prevalence of IPIs in females (22%) was similar to males (24%), which is similar to the study by Gelaw 2013 [47], but in contrast to study by Daryani 2017[116] in Iran. In Iran, report indicated that more females have (30.9%) have IPIs than males (16.5%). The difference might be due to cultural and behavioral difference between the two countries.
The distribution of IPIs in this study was relatively similar in both urban and rural areas. This might be due to absence of proper human waste disposal systems, the shortage of safe water supply, the social and poor environmental or personal hygiene in many unplanned urban areas in Ethiopia in addition to similarity of eating habit and life style of both urban and rural areas of the country. So far, reports from Africa and South Asia countries are con icting. Some were reported higher infection rates of IPIs in rural areas compared to urban areas [124][125][126][127][128] and others reported higher rate of infections in urban children [129]. In fact, comparable data on IPIs in urban and rural settings are very limited. For instance, only 13 studies out of 83 studies included in this meta-analysis were reported prevalence of IPIs in both urban and rural areas and therefore, indicating more work to be done in the future to resolve this issue.
We estimated the geographical distribution and identi ed high risk areas that should be prioritized control interventions, which complement global efforts towards elimination of IPIs infections by 2020. In addition, this work also highlighted the need for survey in areas where data are not available such as Somalia region, Afar region, Harari, Dire Dawa city and Gambella region or scarce (Addis Ababa city and Benishangul-Gumuz region). The essence of current systematic review and meta-analysis of IPIs data analysis among preschool and school-age children in Ethiopian were to support the efforts undertaken to control and eliminate neglected tropical diseasesby nurturing or supplementing useful national epidemiological data. We hope that the ndings of current study provide valuable information to the policymakers, National Health Bureau and other concerned bodies about national and regional distribution and their prevalence in Ethiopia preschool and school-children.
There are a few limitations of the present meta-analysis, which may affect the results. First of all, the review protocol is not registered which could be source of bias. .It is prudent to interpret the results of this study as 37(44.6%) of the included studies were low quality based on our quality assessment criteria. In all of studies included in this review, single stool sample examination were used despite multiple stool samples recommendation for standard diagnosis and therefore, possible underestimation of the prevalence. There is also substantial heterogeneity observed between the studies that affect the interpretation of the results. However, we did metaregression analyses on various sources including geographical distribution, age category and year of publication.
These might comefrom age category (P= 0.002) and year of publication (P= 0.023) but not from geographic distribution (p = 0.56).

Conclusions
Intestinal parasite infections are highly prevalent and well distributed across the regional states of Ethiopia.
Southern and Amhara regional states carry the highest burden. Although school-age children have higher prevalence of IPIs compared to preschool-age children, the prevalence is still unacceptably higher among preschool-age children. We observed a gradual, but signi cant decrease in prevalence of IPIsamong preschool and school-agein Ethiopian in the last two decades with no signi cant difference between males and females. The prevalence in the most recent six years was around 42% compared to 71% in the late 1990s.Place of residence has no effect on the burden of IPIs among preschool and school-age in Ethiopian. Sixteen percent (16%) of preschool and school-age children had concurrent poly-parasitism infections.  Tables Table 1 Characteristics