Effect of Deworming on Health Outcomes among Children Aged 12–59 Months in Tanzania: A Multilevel Mixed Effects Analysis

Introduction Mass deworming of preschool children is a strategy suggested to prevent soil-transmitted helminth infections in most developing countries. Nonetheless, there is a scarcity of data showing the contribution of mass deworming to a child's nutritional status. The purpose of this study was to assess the effect of deworming on nutritional health outcomes (stunting, underweight, and anemia) in children aged 12 to 59 months. Methods A secondary analysis of data extracted from the Tanzania Demographic and Health Survey (TDHS) 2015-16 data was carried out. A total of 7,962 children were included in this study. A multilevel logistic regression was used at a 5% level of significance to determine the individual- and community-level determinants of deworming on health outcomes among children. Results The prevalence of underweight (62.6%), stunting (61.0%), and anemia (61.8%) was higher in children who were not dewormed than those who were dewormed. Female children were more likely to suffer from poor health outcomes (OR = 1.01 and 95% CI = 0.95–1.07) than male children. Children aged 24–35 months and 36–47 months were significantly less likely to suffer from poor health outcomes (OR = 0.89; 95% CI = 0.82–0.97 and OR = 0.88; 96% CI = 0.81–0.96, respectively; p < 0.01). Children from households with unimproved toilets (OR = 1.38 and 95% CI = 1.25–1.52), unimproved water sources (OR = 1.08 and 95% CI = 1.01–1.16), and living in rural areas (OR = 1.02 and 95% CI = 0.91–1.14) had higher odds for poor health outcomes. Conclusion Deworming may be an effective technique for preventing poor health outcomes in children and the risks associated with them, such as poor growth and development.


Introduction
More than one billion individuals in developing countries are infected with soil-transmitted helminths (STH), with roughly one-third of the world's population aficted with at least one STH species [1,2]. Te World Health Organization (WHO) [3] estimates that 270 million preschool children in developing countries are infested with species such as whipworms (Trichuris trichiura), roundworms (Ascaris lumbricoides), and hookworms (Necator americanus and Ancylostoma duodenale). Heavy worm infestation has been associated with malnutrition, in particular stunting, underweight, and anemia in children [4][5][6].
STHs have varied nutritional outcomes to the host as they compete for micronutrient absorption in the small intestine and feed on host tissues such as blood and serum, causing iron and protein loss. Tey also cause maldigestion or malabsorption of nutrients. Moreover, feeding on the contents in the gut including the host's secretions that make up the exoenteric circulation decreases appetite, lowering the food intake of an infected individual [7,8].
Physical growth and cognitive development are significantly afected when children are chronically infected with STH [9]. Despite other factors associated with anemia, such as diet, infections, and genetics, the prevalence of anemia in developing countries has been greatly contributed by intestinal parasite infections among children [10]. Several studies conducted in diferent parts of the world also showed a strong association between STH and iron defciency anemia in children [9,11,12].
To lessen the burden of worm infestation in the community, WHO recommends all preschool children and other risk groups receive periodic pill therapy (deworming) once or twice a year, with the most common being albendazole 400 mg and mebendazole 500 mg. In locations where the prevalence of infection is greater than 20%, deworming is recommended once a year, and twice a year in areas where the incidence is greater than 50% [3]. Te goal of the deworming program is to reduce the number of children with moderate or high-intensity infections, which are associated with poor health outcomes.
Tanzania, like other underdeveloped nations, has a high prevalence of STH parasite transmission; hence, children between the ages of 12 and 59 months undergo deworming twice a year. However, there is a scarcity of data on the efects of the deworming campaigns on the nutritional health outcomes of the targeted age group. Terefore, the purpose of this study was to assess the efect of deworming on nutritional health outcomes in children aged 12 to 59 months. Te study's fndings will be used by government ministries, policy makers, and development partners to improve deworming interventions in the country.

Study Design.
A secondary analysis of data extracted from the Tanzania Demographic and Health Survey (TDHS) 2015-16 data was carried out. Te study methodology is described in detail in the TDHS 2015-2016 published report [13]. In summary, the TDHS used a multistage cluster sampling design in which 608 clusters were selected at the frst stage and 22 households from each selected cluster were sampled at the second stage. Te survey included 10,233 children aged 0-59 months from all regions of Tanzania who were matched with their mothers. Only 7,962 children aged from 12 to 59 months were chosen for this study. A detailed description of the procedure used to select children is given in Figure 1. Te number of samples from each region collected for this study is depicted in Figure 2.

Outcome Variables.
Health outcomes variables (stunting, underweight, and anemia) were the three dependent variables investigated in this study. Based on WHO guidelines, a child is stunted if his or her height for age Zscore (HAZ) is less than −2 SD, and underweight if his or her weight for age Z-score (WAZ) is less than −2 SD. To create a dichotomous variable, stunted or underweight children were assigned 1 and assigned 0 if they were normal. Anemia is defned as a defciency of hemoglobin (Hb) to provide adequate oxygen to bodily tissues. According to the WHO, a child has anemia if his or her Hb level is less than 11 grams per deciliter (g/dL). Informing dichotomous variables, being anemic was assigned 1 and 0 for nonanemic (normal). Households were given scores based on the number and kinds of consumer goods they owned, ranging from a television to a bicycle or car, plus housing characteristics, such as the source of drinking water, toilet facilities, and fooring materials. Tese scores were derived using principal component analysis. Te wealth index variable categorizes the household's wealth status into three classes: poor for the poorest and poor, normal (neutral) for the middle, and rich for the richer and richest.

Explanatory Variables.
Eight explanatory variables were considered in this study based on their association with deworming status. Tese variables were classifed into two groups: individual-level variables and community-level variables.

Individual-Level
Variables. Te child's age (month), sex of child, mother's education level, and mother's age, and type of toilet facility were included as individual-level variables.

Community-Level Variables.
Wealth quantile, type of place of residence (urban and rural), and water source were regarded as community-level variable.

Data Analysis.
Te STATA software, Version 15 (Sta-taCorp LLC, USA), was used for analysis. As part of this analysis, all data were cleaned, processed, and recorded in the appropriate format. Te characteristics of the study population were described using frequencies in the descriptive analysis. A multilevel logistic regression was used at a 5% level of signifcance to determine the efect of individual-and community-level determinants of deworming on three health outcomes (stunting, underweight, and anemia) among children. Te p value <0.05 was considered statistically signifcant. Descriptive statistics were displayed for individual and community variables. Tree models are displayed in this analysis: model I (contains individual variables), model II (contains community variables), and model III (both individual and community variables).

Description of Social-Demographic Characteristics of Study Participants in Association with
Deworming. Te total weighted samples of 7,962 children ranging in age from 12 to 59 months were included in this study (Table 1). Gender was represented equally, but males (42.1 percent) were dewormed more than females. Children aged 12-23 months were higher presented than other age groups (28.1 percent), but the percentage of dewormed children was nearly equal across all age groups. Children who were more dewormed came from a better toilet-equipped household, a wealthy family, had a mother who was older than 30 years, and had secondary or higher education.

Prevalence of Underweight, Stunting, and Anemia and
Association with Deworming in Children. Overall, 15 percent of children were underweight, 39.5 percent were stunted, and 55.8 percent were anemic ( Table 2). Te prevalence of underweight (62.6%), stunting (61.0%), and anemia (61.8%) were higher in children who were not dewormed than those who were dewormed.

Community-Level Variables.
Children from rich families were signifcantly more likely protected from poor health outcomes (OR � 0.69; 95% CI � 0.62-0.76; and p < 0.01), and compared with urban children, rural children had higher odds for poor health outcomes (OR � 1.02 and 95% CI � 0.91-1.14). Lastly, children from households with unimproved water sources were more likely to sufer from poor health outcomes (OR � 1.08; 95% CI � 1.01-1.16; and p < 0.05) than those using improved water sources (Table 3).

Discussion
Tis study found a signifcant association between deworming treatment and anemia among children aged 12 to 59 months who were involved in the study. However, there was no signifcant association between deworming treatment and being underweight or stunted. Tis study found a lower likelihood of anemia in dewormed children compared to their counterparts. Studies have found that children who received deworming treatment had signifcantly lower levels of anemia than those who did not [14][15][16]. Tis is likely due to the fact that deworming can reduce the amount of nutrients lost to parasitic infections, allowing more nutrients to be available for hemoglobin synthesis, and other processes involved in the production of healthy red blood cells. In addition, deworming can reduce the risk of infection and infammation, which can also contribute to anemia [17]. Our fnding compares well with previous studies conducted in Zanzibar, Tanzania, and Tailand, which found signifcant improvements in hemoglobin concentration and a decrease in anemia prevalence in children after deworming treatment [18,19]. Such a dramatic change in the anemic condition after deworming treatment strongly suggests that the anemia in the study subjects was primarily caused by hookworm infection, rather than an iron defciency caused by poor nutrition. Parasites live in a dynamic relationship with their hosts who provide all the energy and nutrients required, resulting in reduced food intake and poor nutrition of the host, causing changes in the intestinal walls, thus it causes inefcient digestion and absorption. Heavier infections can cause a range of symptoms including intestinal manifestations (diarrhea and abdominal pain), malnutrition, general malaise and weakness, and impaired growth and physical development [20]. Infections of very high intensity can cause intestinal obstruction that should be treated surgically. For example, Necator americanus (hookworm) have shown to reduce iron absorption, and in some instances to be associated with iron defciency anemia [21]. Chergui and colleagues reported severe iron defciency anemia due hookworm infection in a 34-year-old Pakistani patient with a barefoot walking habit. A barefoot walking is very common in young children in sub-Saharan countries [22]. Other studies have suggested that deworming may also reduce anemia indirectly [23,24]. Tis can be seen in areas with a high prevalence of intestinal worms, where anemia is prevalent due to poor nutrition and low socioeconomic status, and not due to the direct efect of the parasites. In such areas, deworming may lead to improved nutrition, and, in turn, improved anemia rates. Tus, in addition to encouraging nutrition education and feeding practices, periodic deworming may be an efective technique for preventing anemia in children and the risks associated with it, such as fatigue, headaches, and poor growth and development. No signifcant association was observed between deworming with neither stunting nor underweight. Similar results were reported in previous studies on the efect of deworming on preschool children [25,26]. Tere is some evidence that deworming can reduce stunting in under-fve children. Studies have shown that deworming programs can lead to improved nutritional status, increased body weight and height, and increased cognitive development. Studies conducted in India [27], Peru [12], and Uganda [28] found statistically signifcant improvement of weight in children who were dewormed every 6 months compared with their counterparts. Likewise, another study found a signifcant increase in height and weight after deworming, which suggests positive efects of deworming in reducing the risks of stunting and underweight in children [29]. Moreover, previous studies found signifcant efects of deworming on reducing risks of stunting in children [9,30]. However, the evidence is not defnitive and further research is needed to determine the full impact of deworming on stunting in under-fve children. While deworming alone is not enough to address the problem of stunting, it is an important intervention that can help to reduce the prevalence of stunting in children.
Te study showed that children age and mother's age had association on health outcomes. Older children were less likely to sufer from poor health outcomes; likewise, children from older mothers had also lower risk of sufering from poor health outcomes. Children less than 2 years old are more vulnerable to poor nutritional health outcomes because their bodies are still developing and their immune systems are not as developed as older children [31]. In addition, their bodies are more sensitive to changes in nutrition because their developmental processes are still in fux. Te reason for greater protection among children over 2 years up to 5 years might be their bodies are better able to absorb and metabolize nutrients. Tey have more developed digestive systems, and their organs, such as the liver, are better able to process and breakdown food. Tis allows them to absorb more of the nutrients from food and helps to prevent malnourishment.
Our study observed gender diferences on the likelihood of sufering from poor health outcomes. Females had higher odds of sufering from poor health outcomes than males. Tis gender diference might be attributed due to biological factors as males tend to have higher levels of insulin-like growth factor-1 (IGF-1) than females, which is linked to an enhanced ability to take in nutrients from their diet [32]. In addition, males have been observed to have greater bone density than females [33], providing them with a shield from malnourishment. Moreover, males have been found to have a higher metabolic rate, allowing for more efective processing and absorption of nutrients.
Te study also showed an association between socioeconomic status (wealth quantile, level of education, and type of place of residence) on health outcomes. However, there were disparities in how each of this determinants of deworming infuence health outcomes. While rich wealth quartile and higher level of education reduces the odds ratio of children sufering from poor health outcomes, living in rural areas increases the likelihood of children sufering from poor health outcomes. Socioeconomic factors, such as poverty and income, have been shown [34] to have an impact on the efectiveness of deworming with nutrition health outcomes. Poor families may lack the resources to access deworming treatments and adequate nutrition, resulting in a higher prevalence of worm infections and subsequent health issues. Furthermore, environmental factors, such as access to clean water and sanitation, can also be infuential [35]. Poor sanitation can facilitate the spread of worm infections, while clean water can help to reduce the risk of contamination and reinfection [35]. Access to healthcare and education is also a critical factor in successful deworming with nutrition health outcomes [36]; without proper education about the risks and efects of worm infections, people may not recognize the need for deworming treatments. In addition, dietary practices can also afect these outcomes; a balanced, nutritious diet can help to reduce the risk of worm infections, while an unhealthy diet can lead to an increase in these infections [37].
In 2001, the World Health Assembly (Resolution number: WHA54.19) requested all member states with intestinal worm infestations of more than 20% to deworm all under-fve children once a year. In addition, countries with worm infestations of 50% or more were requested to pursue deworming of all children under fve years old twice a year to eradicate or minimize the intensity of worms and the consequences of worm infestation [38]. In response, Tanzania implemented mass drug administration to all children between 12 and 59 months, including twice-yearly vitamin A supplementation [39]. However, due to the lack of drug category data in the Tanzania DHS, it was not possible to subdivide the sample into groups according to the type of deworming drug used and correlate them with the outcomes. Mebendazole 500 mg was the drug of choice during mass drug administration among children under fve in Tanzania for simplicity during service delivery, recording, and reporting.
Te selection of a nationwide representative sample provided good statistical power and a large generalization impact in this study. Tis study, however, is subject to several limitations. Te survey's cross-sectional design limits the study's ability to fnd a cause-and-efect association. In addition, the responses given by mothers/caregivers regarding reporting deworming treatment to their children are sometimes based on their ability to recall and could be recall bias. Terefore, another large study to account for the observed constraints is strongly urged.

Conclusion
Tis study found strong association of deworming and anemia; dewormed children were less likely to be anemic than their counterparts. Terefore, regular monitoring and evaluation of the efectiveness and impacts of deworming programs are strongly urged to inform the government and decision-makers on how to continue or strengthen the program. 6 Journal of Nutrition and Metabolism Abbreviations HAZ: Height for age Z-score STH: Soil-transmitted helminths TDHS: Tanzania Demographic and Health Survey WAZ: Weight for age Z-score.

Data Availability
To access TDHS 2015 dataset, you must register in the repository of the DHS Program and make a request.

Ethical Approval
Te Demographic and Health Survey (DHS) program granted authorization to conduct this research. Te TDHS was approved by the Ethical Review Committee of the National Institute for Medical Research (NIMR), Tanzania. All procedures were conducted according to the guidelines laid down in the Declaration of Helsinki of 1975.

Consent
Written and verbal consent was obtained from the parents or guardians of all children living in the interviewed households. Te risks and benefts of the study were clearly explained to the participants before they signed the consent.

Conflicts of Interest
Te authors declare that there are no conficts of interest.