Reduced uptake of mass treatment for schistosomiasis control in absence of food: beyond a randomized trial

The goal of the Ugandan national schistosomiasis control program is morbidity control through regular mass treatment in endemic areas [1]. Annual school-based mass treatment with praziquantel is the cornerstone for schistosomiasis control among school-aged children. The school approach is based on the premises that it is cost-effective to deliver interventions through the school system because schools are widely distributed and that school teachers can assist to administer the drugs to the children [2–5]. The drawbacks of this strategy have been documented in many parts of the country. The reliance on volunteer teachers to distribute treatment, the fear of side-effects of praziquantel, low school attendance rates and the social, economic and political context in which mass treatment is rolled out profoundly affect the uptake of drugs among the targeted population [6–9]. In some locations, uptake of treatment has been found to be low [8–11]. The target is to treat at least 75 % of school-age children at risk of morbidity [12]. In a particular study conducted in Jinja district, less than 30 % of the school children took praziquantel during mass treatment in 2011. The fear of treatment, inadequate health education and lack of teacher support were some of the factors thought to influence the uptake [11]. In an effort to increase the uptake of treatment in 2012, the national control program motivated the teachers to distribute treatment through provision of incentives and intensified supervision with little success [13].

Praziquantel should be concurrently administered with food to mitigate the side effects of the drug and increase its uptake [14–16]. Studies assessing the use of food incentives have shown improved participation of children in health programs for treatment of schistosomiasis, HIV/AIDS and other diseases [16–19]. Furthermore, the use of food is associated with improved treatment outcomes and education benefits among school children [17, 20, 21]. In Uganda, the school feeding policy requires that parents take responsibility for feeding their children while at school [22]. However, due to the prevailing poverty in many parts of the country, most parents cannot afford to meet the cost of a daily meal for their children while at school [23]. In areas where annual treatment with praziquantel for schistosomiasis control is provided, most children take the treatment on an empty stomach and experience side effects [24, 25] and as such, reject the drug during the subsequent mass treatment programs [9, 26].

Strategies for improving uptake, such as provision of food to mitigate the side effects of praziquantel and motivate children to take treatment are required. Our study conducted in 2013 demonstrated the effectiveness of a pre-treatment snack on the uptake of praziquantel among school children [27]. This study compares the 2013 uptake with the 2014 uptake when no snack was provided. In addition, the reported side effects attributable to praziquantel and prevalence and intensity of schistosomiasis infection are compared.

This study found that the 2014 uptake of praziquantel was lower than the 2013 uptake although the prevalence and intensity of S. mansoni infection was unchanged between the years. The reported frequency of side-effects in 2014 was higher than that in 2013. Knowledge of schistosomiasis prevention was lower in 2014 than in 2013.

The observed decrease in uptake of treatment in 2014 may be attributable to lack of food for mitigating the side-effects of praziquantel. During the 2013 mass treatment, food to alleviate the side-effects and motivate the children to take treatment was provided to children with high levels of success [27]. The fear of side-effects as a major reason for non-uptake of praziquantel has been previously reported [8, 11, 13]. Food high in carbohydrate content increases the absorption of praziquantel form the gastro-intestinal tract, enhances its bioavailability and lowers the odds of side-effects [14–16]. During the 2014 mass treatment, only 54.4 % compared to 92.8 % of the children in the snack schools in 2013 reported to have taken food prior to mass treatment, the majority reporting maize porridge as the major type of food taken. The other types of food reported included pancakes, maize cobs and dry tea. This implies that a large proportion of children in 2014 took treatment on an empty stomach with the risk of widespread side-effects. The drug distribution strategies in the non-snack schools in 2013 and 2014 were similar, with no specific measures to mitigate the side-effects and motivate children to take treatment on both occasions. This probably explains the unvarying uptake levels and occurrence of side-effects among children in this group. These data suggest that the reasons for the low uptake identified in our previous studies [11, 13, 26] such as, inadequate information about schistosomiasis prevention, insufficient preparation and facilitation of teachers to distribute treatment and the fear of side-effects of praziquantel, especially when the drug is taken on an empty stomach are probably accurate and the measures suggested, such as provision of food in combination with education messages prior to treatment [27] are necessary to maintain high treatment coverage. A detailed cost-effectiveness analysis of provision of indigenous, locally available and relatively low cost food, such as maize porridge, during mass treatment should be undertaken and if found cost-effective, provision of food should be integrated into school-based mass treatment. A multi-pronged strategy for provision of food by the national control program, parents or the Government could be used.

The prevalence and intensity of S. mansoni infection after mass treatment in 2013 and 2014 were unchanged in both groups of schools. Although the realized uptake in both the non-snack (70.4 %) and the snack schools (78.0 %) during the 2014 mass treatment was lower than the 2013 uptake (78.7 and 93.9 %), the 2014 uptake was adequate to maintain the levels of infection but inadequate to significantly reduce the prevalence rates and intensity of the infection. In high transmission areas, chemotherapy with praziquantel is effective in reducing morbidity but the prevalence and intensity of infection return to pre-treatment levels within a short time if no other means of control are applied, even when treatment coverage is high [33]. In the study area, the majority of the children frequently visit the lake to fetch water, bathe, wash, fish and to swim [10, 11] and are thus at high risk of infection and re-infection. Sustained drop in infection can be achieved through a combination of interventions including preventive chemotherapy, health education, cessation of poor human sanitation practices and improved access to safe water [34, 35]. Each of these strategies is important but not sufficient when applied in isolation. Inadequate resources and capacity for such measures are major obstacles to sustainable schistosomiasis control in developing countries [36]. In the study area, school-based mass treatment with praziquantel is the mainstay for schistosomiasis control among school-age children. The challenges associated with this strategy have been discussed elsewhere [6, 7, 37, 38].

Knowledge of schistosomiasis prevention in both groups of schools in 2014 was considerably lower than that in 2013, a manifestation of the insufficient health education provided in 2014. Prior to the 2013 mass treatment, education messages tailored to the knowledge gap in schistosomiasis prevention were provided to all children in both groups of schools with high levels of knowledge registered in the schools. In 2014, less than a half of the children in both the snack and non-snack schools reported to have been sensitized about schistosomiasis prior to mass treatment. As such, a significant reduction in the proportion of children with adequate knowledge of schistosomiasis prevention was noted in both groups of schools. Health education and other behavioural change interventions are effective strategies for increasing compliance to treatment for schistosomiasis [39–41]. In the absence of these interventions, there is a risk that the targeted populations may resist treatment [9, 39].

Children who participated in both studies were selected at random. It is possible that some of the children examined in 2013 could have been re-examined in 2014 and provided similar responses on both occasions. However, the correlation between self-reported uptake and S. mansoni infection and intensity validated the self-reported uptake as accurate. A negative linear relationship between uptake of praziquantel and prevalence as well as intensity of S. mansoni infection was observed: In schools with high uptake, the prevalence and intensity of S. mansoni infection was much lower than in schools with low uptake. Secondly, the Kato-Katz technique adopted for this study analyses a small amount of stool (41.7 mg) and therefore has a relatively low capacity to detect eggs from specimens of low intensity infections [30, 42]. The sensitivity of the method was increased by examining two stool samples from each child and preparing two thick stool smears from each sample.

This study shows that in the absence of food to motivate children to take treatment and to mitigate the side-effects of praziquantel, uptake of praziquantel reduces and the side-effects of the drug increase. Thus, strategies for maintaining high treatment coverage are needed. Such strategies should include continued sensitization and education of the children and provision of food at school to mitigate the side-effects attributable to praziquantel treatment and motivate children to take treatment.