Intestinal schistosomiasis among schoolchildren in Sana’a Governorate, Yemen: Prevalence, associated factors and its effect on nutritional status and anemia

Intestinal schistosomiasis is a neglected tropical disease, causing morbidity and mortality in tropical and subtropical countries. Despite the frequent implementation of mass drug administration with praziquantel, the reinfection with Schistosoma mansoni is still common in Yemen. In addition, there is a scarcity of information on the impact of S. mansoni on nutritional status and anemia among schoolchildren. The present study aimed to determine prevalence and risk factors of intestinal schistosomiasis and investigate its impact on nutritional status and anemia among schoolchildren in Sana’a Governorate, Yemen. It was conducted in 2018 on 445 schoolchildren aged 5–15 years. Biodata, socio-economic, demographic, behavioral and environmental data were collected using a standard questionnaire. S. mansoni was identified and quantified by microscopic examination of Kato-Katz fecal smear. Hemoglobin concentration and anthropometric measurements were estimated using standard methods. The prevalence of S. mansoni was higher in Al-Haimah Al-Dakheliah (33.9%) than Bani Mater (1.4%). Household without tap water (Adjusted Odds Ratio (AOR) = 2.9, 95% Confidence interval (CI): 1.12, 7.55, P = 0.028) was the independent risk factor of the infection. The prevalence of wasting and stunting was 25.0% (95%CI: 21.2%, 29.2%) and 45.8% (95%CI: 41.2%, 50.5%), respectively. The prevalence of underweight among schoolchildren aged 5–10 years was 27.3% (95%CI: 21.9%, 33.4%). The prevalence of anemia was 31.7% (95%CI: 27.5%, 36.2%) with 0.5%, 21.1% and 10.1% being severe, moderate and mild anemia, respectively. S. mansoni (AOR = 4.1, 95%CI: 2.16, 7.84, P < 0.001) and early adolescence (AOR = 6.8, 95%CI: 4.26, 10.82, P < 0.001) were independent predictors of stunting among schoolchildren. The early adolescent schoolchildren (AOR = 3.1, 95%CI: 1.86, 4.97, P < 0.001) and children from families with low (AOR = 2.1, 95%CI: 1.01, 4.15, P = 0.046) or moderate wealth (AOR = 2.3, 95%CI: 1.11, 4.77, P = 0.026) were significantly more wasted. Early adolescence (AOR = 1.8, 95%CI:1.14, 2.78, P = 0.011), female (AOR = 1.6, 95%CI: 1.03, 2.43, P = 0.038) and Al-Haimah Al-Dakheliah District (AOR = 3.4, 95%CI: 1.20, 9.55, P = 0.021) were independent risk factors for anemia. The study findings indicate highly focal prevalence of schistosomiasis in Sana’a Governorate with a public health significance that varies from low to high risk. Approximately half of schoolchildren were stunted, which was associated with S. mansoni infection and early adolescence. One quarter of schoolchildren were wasted with early adolescent schoolchildren and children from poor families being at high risk of wasting. Anemia was a moderate public health threat affecting the female and the early adolescent schoolchildren. The study suggests the implementation of control measures to combat schistosomiasis and integrated diseases control programmes to improve the health status of schoolchildren in Sana’a Governorate.


Introduction
Human schistosomiasis is a neglected tropical disease caused by Schistosoma species and occurs mainly in tropical and sub-tropical countries [1]. It causes severe morbidity and mortality with an estimated global burden of 1.4 million disability-adjusted life-years (DALYs) [2]. Schistosoma species with high global prevalence include S. haematobium (urogenital schistosomiasis), S. mansoni and S. japonicum (intestinal schistosomiasis) [1]. Intestinal schistosomiasis in schoolchildren compromises growth, physical fitness, cognitive function and educational achievement and causes anemia [3][4][5].
In Yemen, schistosomiasis has been a public health problem since 1922 [6] with a patchy distribution and different infection rates, ranging from 15% to 100% [7][8][9][10][11][12][13][14]. A combined Yemen-WHO project for controlling schistosomiasis was set up in 1973, which estimated that 25% of the population were infected with S. mansoni and/or S. haematobium [15,16]. After implementing several campaigns of school-based mass drug administration (MDA) with praziquantel, the prevalence of S. mansoni at country level dropped to 2.5% with a district-based prevalence ranging from 0.0 to 35.7% [17]. In the nationwide survey conducted in 2017, three years after the previous survey, the prevalence of S. mansoni increased to 7.4% [18]. Malnutrition and anemia are other threats affecting schoolchildren in Yemen where 59%, 47% and 18% of school-aged children were found stunted, underweight and anemic, respectively [19]. However, there is a paucity of information about the impact of S. mansoni on the nutritional status and anemia among schoolchildren in Yemen [20]. Thus, the present study aimed to determine prevalence of S. mansoni, identify factors associated with the infection and its impact on nutritional status and anemia among schoolchildren in rural communities of Sana'a Governorate, Yemen.

Study area, design and subjects
This is a cross-sectional study conducted in the rural areas of Sana'a Governorate, Yemen. Schoolchildren aged 6-15 years were the study population. Children who had taken iron, nutritional supplements or anti-parasitic drugs in the last six months prior to the study were excluded.

Sample size and sampling strategy
The minimum sample size required for the study was 358 schoolchildren which was calculated by Epi Info | CDC (https://www.cdc.gov/epiinfo/index.html)) using the following parameters: 95% confidence interval, ± 5% precision and the highest recently reported prevalence of S. mansoni (37%) [17]. However, 445 schoolchildren were enrolled in the study to replace participant for not providing fecal sample. A multistage sampling approach was used for selecting schoolchildren where two districts from rural areas of Sana'a Governorate were randomly selected, followed by random selection of one school from each district. Children from each school were selected by systematic random sampling from the students record until the required sample size was obtained. If a selected child refused to participate or was not eligible, he/she was replaced by the next student in the record. The number of students selected from each school was proportional to the size of the school.

The study questionnaire
Biodata, socio-economic, demographic, behavioral and environmental data were collected using a pre-designed, structured questionnaire through a face-to-face interview. The questionnaire included questions about durable items, animals and agricultural land owned by households; household's source of drinking water; sanitation coverage; father and mother education; and the number of household's members.

Parasitological investigations
A single fresh fecal sample was collected from each participant in a dry, clean plastic container, labeled with the child's name and identification number. At the field, a Kato-Katz thick fecal smear was prepared from each fecal sample and the rest of feces were preserved in 10% formalin. The Kato-Katz thick fecal smears were then transported to the Parasitology Laboratory in the Faculty of Medicine and Health Sciences, Sana'a University and examined for S. mansoni [21]. The intensity of S. mansoni was classified into light (1-99 EPG), moderate (100-399 EPG) and high intensity (� 400 EPG) [22]. The public health significance of the prevalence of S. mansoni was classified into high risk (�30%), moderate risk (�10 and <30%) and low risk (<10%) as suggested by the national control strategy [17].

Anthropometric measurements
For anthropometric measurements, standing height of each child was measured to the nearest 0.1 cm using a portable stadiometer (Seca, model 208) and his/her weight was measured to the nearest 0.1 kg using a digital weight scale. The age of each participant was retrieved from the birth certificate or school records. The collected measures were used for calculating height-forage z-score (HAZ), weight-for-age z-score (WAZ) and BMI-for-age z-score (BAZ) using the WHO AnthroPlus software for the global application of the WHO reference 2007 for 5-19 years [24]. The WHO reference data for WAZ used by the WHO AnthroPlus software were for age � 10 years; therefore, underweight was estimated for children aged 5-10 years old. The nutritional indicators for school-age children were defined as follows:

Statistical analysis
Data were analyzed using IBM SPSS Statistics for Windows, version 23.0 (IBM Corp., Armonk, NY, USA). The wealth indices were determined using the principal component analysis (PCA) of durable items, animals and agricultural land owned by households. The

Nutritional indicator
Cut-off Z-score constructed PCA-based scores of households were divided into five quintiles and three wealth categories, where households' residents with the lowest 40%, the middle 40% and the highest 20% of household wealth quintiles were classified as low, middle and high, respectively [25]. Categorical variables were presented in frequencies. The association between independent and dependent variables was tested using Pearson's chi-square with reporting odds ratio (OR) and its corresponding 95% confidence interval (CI). Multivariable analysis using entry binary logistic regression model was conducted including all predicting variables and the adjusted OR with its corresponding 95%CI were reported. P-value of <0.05 was considered significant.

Ethics statement
The study protocol was approved by Research and Ethics Committee (REC) of the Faculty of Medicine and Health Sciences, Sana'a University. Approval of school headmasters/ headmistresses was also taken after explaining the significance of the study. Each child was voluntary involved after receiving information in a way that the child can understand and give his/her assent. No informed consent was obtained from child's parents/guardians, although they were informed about the study and had the right to refuse the participation of their child. Anonymity, dignity and privacy of the child and his/her family were protected. Table 1 summarizes the characteristics of participants. A total of 445 schoolchildren were enrolled in this study. Their age ranged between 5 and 15 years with a mean of 10 ± 2.54. The majority of children (70.6%) were in the age group of 5-11 years. About 82% of the children belonged to families with more than 5 members. More than half of the children were living in houses without proper sanitation coverage (no toilet or flush/pour flush to open area) and about one-third had unimproved source of drinking water. Although no much difference in the characteristics of the study participants between the two districts, the majority of schoolchildren in Al-Haimah Al-Dakheliah District are living in houses without access to improved sanitation.

Prevalence and factors associated with stunting, wasting and underweight
The prevalence of stunting among schoolchildren was 45.8% with 26.3% of the children being severely stunted while the prevalence of wasting was 25% with 9.7% of the children being severely wasted. Children aged 11-15 years had significantly higher rates of stunting and wasting than children aged 5-10 years. Among schoolchildren aged 5-10 years, 27.3% of them were diagnosed as underweight and 10.8% were classified as severe underweight (Table 4).

Discussion
The present study indicated focal prevalence of S. mansoni among schoolchildren in Sana'a Governorate. At district level, the study placed Al-Haimah Al-Dakheliah and Bani Mater districts at high and low risk of schistosomiasis (33.9% and 1.4%, respectively). The presence of foci with high infection rates, although the pressure of MDA campaigns, can be explained by the high reinfection rate of S. mansoni. A recent study conducted in Ethiopia reported high reinfection rate of S. mansoni after 6 months of treatment with praziquantel [26]. The reinfection with S. mansoni was found to be affected by socioeconomic status, level of education of the household head and the baseline heavy infection [27], which may justify the variation in the prevalence of S. mansoni between the two districts. These findings, in turn, suggest that MDA campaigns should be integrated with additional measures to control schistosomiasis.

PLOS NEGLECTED TROPICAL DISEASES
Intestinal schistosomiasis among schoolchildren in Sana'a Governorate, Yemen Multivariable analysis identified having no tap water at home as an independent risk factor of S. mansoni in Al-Haimah Al-Dakheliah District. This observation could be explained by the possibility of children's responsibility of bringing household's water, a common practice in Yemen, which increased their contact with unsafe water and made them prone to S. mansoni infection [28,29]. The result suggests an integration of MDA of praziquantel and the delivery of a community-based WASH programme as an effective approach for combating schistosomiasis in these communities. The positive impact of WASH intervention on deworming programmes has been well evidenced [30,31]. The nutritional status of schoolchildren in Yemen has been neglected despite its significant impact on cognitive and educational achievement [5]. In the present study, the prevalence of stunting, underweight and wasting among schoolchildren aged 5-15 years was 45.8%, 27.3% and 25%, respectively. The study reported lower prevalence of stunting and underweight and five-times higher prevalence of wasting compared to stunting, underweight and wasting reported in previous studies conducted among schoolchildren in Al Mahweet and Sada'ah governorates, Yemen [19,20]. The prevalence of stunting and wasting were higher among schoolchildren aged 11-15 years than those aged 5-10 years. These findings are consistent with previous studies conducted in Pakistan [32], Tanzania [33] and Madagascar [34]. The increased prevalence of stunting and wasting with age could be explained in part by the accumulated exposure of the older children to childhood diseases and inadequate diets [35]. Schistosoma mansoni is an independent risk factor of stunting among schoolchildren in Sana'a Governorate. The association between S. mansoni and stunting was reported in different studies [4,36,37].
Underweight takes into account both acute malnutrition (wasting) and chronic malnutrition (stunting). In the present study, a significant association between S. mansoni and underweight was found using univariable analysis although the multivariable analysis model did not confirm this association. Schoolchildren belonging to families with poor and middle wealth indices were at high risk of being acute malnourished. This finding is consistent with previous reports from Ethiopia [38] and India [39], which could reflect the inadequate feeding among children from families with low wealth indices.
The prevalence of anemia represents a moderate and severe public health problem among schoolchildren in Bani Matar and Al-Haimah Al -Dakheliah districts, respectively. Although the causes of anemia in the present study have not been identified, iron deficiency is one of the primary causes of anemia in the Yemeni communities [40]. The reason behind the high prevalence of anemia in Al-Haimah Al -Dakheliah District is not clear, although it may be attributed to socioeconomic status: 90% of the children belonged to families with moderate and poor wealth indices. Schoolchildren aged 11-15 years were at two times higher risk of being anemic compared to younger age group. This finding is consistent with previous studies conducted among children in different countries [41][42][43][44][45][46], which could be explained by the hyperactivity during this age together with high demand of micronutrient and limited consumption of a variety of food sources due to the household food insecurity [47], which can be reduced by school feeding [48,49]. The gender female was also an independent risk factor of anemia, which is in line with previous studies [50,51]. It is noteworthy that anemia among schoolchildren may lead to impaired cognitive function [52]. No significant association was found between S. mansoni and anemia, which is consistent with previous studies conducted elsewhere [28,33].
The present study is limited by the low number of districts and schools enrolled in the study, which prevents the conclusion about the overall prevalence of schistosomiasis at governorate level because the disease is highly focal, although study findings are consistent with the results of the latest nationwide survey. However, the study sample size and design are appropriate to assess the association between schistosomiasis and nutritional status of schoolchildren in Sana'a Governorate.
In conclusion, the study findings showed highly focal prevalence of schistosomiasis in Sana'a Governorate with a public health significance that varies from low to high risk. Schoolchildren living in houses without tap water are at high risk of the infection. Schoolchildren harboring the parasite and early adolescent children had high prevalence of stunting. Besides, early adolescent schoolchildren and children belonged to families with middle or poor wealth were wasted. Anemia is a moderate public health threat with early adolescent and female schoolchildren, being at higher risk. The study findings suggest adopting integrated control measures for the control of schistosomiasis such as MDA and WASH, and integrated diseases control progarmmes for improving the health status of schoolchildren.