Patient journey and resources mapping to implement a praziquantel mass drug administration program for children aged 5 years and below in resource-limited settings

All the studies that we reviewed reported that PZQ is efficacious against schistosomiasis in children under 5 years. The lowest PZQ dose that was efficacious against schistosomiasis in this age group was 20 mg/kg [26, 27]. All the studies reported on the PZQ dose of 40 mg/kg to treat schistosomiasis in this age group. Three studies reported the difference in PZQ efficacy observed between the use of a PZQ dose of 40 mg/kg and that of 60 mg/kg in the treatment of schistosomiasis in children aged 5 years old and below [26, 28, 29].

All the studies reviewed stated that PZQ is safe for use in the treatment of schistosomiasis in children aged 5 years old and below. The highest safe dosage of PZQ reported was 60 mg/kg [26, 27]. The difference in PZQ efficacy observed between the use of a PZQ dose of 40 mg/kg and that of 60 mg/kg in the treatment of schistosomiasis in children aged 5 years old and below was insignificant [26, 28, 29]. All the studies reported that there were no serious adverse events reported after treating schistosomiasis in children aged 5 years and below with PZQ doses of between 20 to 60 mg/kg. The WHO-recommended dose of 40 mg/kg should be used to treat schistosomiasis during schistosomiasis control MDA programs for children aged 5 years old and below.

All the studies followed the same treatment sequence: enrolment of children into the program, clinical examination, diagnosis, weight and height measurements, and treatment and the monitoring of side effects. Enrolment involved, acquiring consent from parents, recording and clinically examining all the children that participated in the study to make sure that they were safe to receive PZQ treatment. Children who were considered safe for treatment were those who were generally well [13, 14, 24, 25, 33, 34], had no recent illness [33], were not suffering from or receiving treatment for tuberculosis (TB) [33], did not have malaria [13], had not undergone a major surgical procedure [33], were not suffering from a fever [31, 33], and did not have a history of adverse drug reactions [31]. The appropriate interventions were provided to the enrolled children who were ineligible for PZQ treatment based on ill health.

Diagnosis of schistosomiasis was done in all the studies to determine baseline prevalence and intensity in the children before treatment. Weight and height [16, 26, 32] measurements were then done to determine the required dose of PZQ to treat children. Administration of PZQ included feeding the children to reduce side effects [30] and to increase the assimilation of PZQ [14, 34], making the PZQ palatable for the children by breaking or crushing the tablet and mixing it with a sweeter and feeding the tablets to the children. After orally taking the tablet, the children were monitored for side effects. The most immediate side effect that was observed was vomiting the tablet within the first 20–60 min [25, 29], in which case the tablet was re-administered to the children. Other side effects were recorded, and appropriate treatment was provided to the children.

Using the processes carried out in the 13 clinical studies to treat schistosomiasis in children aged 5 years and below, we mapped a patient journey that could be used to implement a schistosomiasis control MDA program for this age group (Fig. 2). In the PZQ MDA patient journey, diagnosis of schistosomiasis could be limited to a sample of the children before for surveillance purposes. The collection of biological specimens for diagnosis could be done before the clinical examination of the children.

The materials that were used to treat schistosomiasis in children under 5 years old in the studies are listed in Table 2. In the same table, we have proposed materials that could be used in a schistosomiasis MDA program for children under 5 years old in resource-limited settings. Registers were used to enroll children in the clinical studies. For a schistosomiasis control MDA program for children under 5, we recommend electronic registers that are embedded in electronic tablets. The Kato-Katz and schistosomiasis urine filtration kits [24‐27, 29, 30, 33, 35] were the most used materials to diagnose Schistosomiasis mansoni and Schistosomiasis haematobium, respectively. The stools and urine for diagnosis were collected in specimen containers [31]. In serological tests, point-of-care circulating cathodic antigen (POC-CCA) [25, 26, 32], soluble egg antigen enzyme-linked immunosorbent assay SEA-ELISA [32], microalbumin reagent strips [33], and urinalysis dipsticks [33] were also used to test for schistosomiasis in the children. Questionnaires were used for diagnosis [4, 14, 16, 24, 26, 27, 29, 32, 33]. We recommend the use of questionnaires and urine dipsticks for the diagnosis of urinary schistosomiasis and the POC-CCA for the diagnosis of intestinal schistosomiasis for disease surveillance in schistosomiasis control MDA programs for children aged 5 years and below. Questionnaires and the Child Health Booklet [14] were used for clinical assessments. We also recommend that both be used for clinical assessments in the schistosomiasis control MDA programs for children aged 5 years and below. Some of the studies that we reviewed reported using weight scales, while others used stadiometers [24, 32] and one used dose poles [32] to obtain the anthropometric measurement that were used to calculate the dose amount of PZQ. We recommend the use of the dose pole and/or tape measures to make these measurements in schistosomiasis control MDA programs for young children.

Bread and juice [13, 26, 29, 30, 33, 34], millet wafer [14], and porridge [14] were the food items that were used in the studies we reviewed. PZQ tablets were crushed with spoons [29] or pestle and mortar [26, 27] to make them small enough for the children to take in. The studies used honey and sugar [24], juice, and syrup flavoured water as sweeteners [13, 26, 29, 30, 33, 34] to mask the bitter taste of PZQ. We recommend that children aged 5 years old and below should be fed with bread and juice or instant porridge during schistosomiasis control MDA programs for this age group. We recommend the use of tablets that are crushed with a pestle and mortar, with juice as the sweetener for use in these MDA programs.

Some of the studies reported using schools [29, 31, 33], early childhood development (ECD) centers [33], healthcare centres [13], clinics [32], and churches [13] as sites where the children were recruited. The schools were used as treatment centres in studies that involved comparisons between children that were aged 5 years old and below (of preschool aged children (PSAC)) and school-aged children (SAC) [33]. The ECD centres that are reported on in the studies were attached to the schools where the SAC participants were found [33]. We recommend the use of schools and clinics as treatment centres for schistosomiasis control MDA programs for children aged 5 years old and below.

The human resources that took part in the clinical aspects of the studies were from a variety of healthcare professions. These medical staff included pediatricians [31], medical doctors [14], nurses [29], and laboratory technicians [26, 27]. Some studies did not specify the professions of the clinical human resources only indicating that medical staff, clinicians, or health officers were part of the study. One study stated the involvement of community leaders and community drug distributors [32] as part of their human resources. We recommend nurses to be the healthcare professionals that implement the schistosomiasis control MDA programs for children aged 5 years old and below.

Some of the studies reported the use of the current WHO-approved 600 mg PZQ dose tablet formulation as a challenge when treating schistosomiasis in children aged 5 years old and below, especially when implementing a large-scale treatment program [26, 30, 36]. They recommended that a variation of this formulation with three partitions that make it possible to split the tablet into four pieces of 150 mg each should be used when treating schistosomiasis in children aged 5 years old and below to ensure correct usage of PZQ to treat schistosomiasis in these children [32]. The studies proposed that a pediatric formulation should be developed, and that the PZQ pediatric formulations could be an orally dispensable tablet [26] or a PZQ syrup [14].

The patient journey for a PZQ MDA program for children aged 5 years and below could follow the sequence: enrolment of children, clinical examination, weight and height measurements, treatment, and the monitoring of side effects for all the children. This is in line with recommendations of the WHO that individual diagnosis of schistosomiasis before treatment is not required before treatment during an MDA program [21]. The studies we reviewed diagnosed all the children to determine the prevalence of schistosomiasis in the children that are aged 5 years and below and also to determine the efficacy of PZQ in treating schistosomiasis in these children. The diagnosis of schistosomiasis in the MDA program is important to determine the baseline prevalence and burden of infectivity of schistosomiasis in the children for monitoring and evaluation [37]. Diagnosis of schistosomiasis in a schistosomiasis control MDA program for children aged 5 years and below for monitoring and evaluation could be done on a random sample of the children soon after they have been enrolled into the treatment program [38]. In some cases, the baseline prevalence and infection intensity could be done separately from the MDA program during disease surveillance programs making the treatment process to move directly from enrolment of the children to clinical assessments [39]. The disease surveillance programs when present could be used to monitor and evaluate the schistosomiasis control MDA programs for children aged 5 years and below.

The Donabedian framework refers to resources as structural components of a healthcare system [22]. The resources that are required to implement a schistosomiasis control MDA program for children aged 5 years and below should be field applicable to the settings in which the MDA program will be implemented [40]. Most of the places where schistosomiasis is endemic are economically disadvantaged and therefore suffer from resource constraints. We used relative cost and ease of access to select the resources that we recommended to be the best for use in a schistosomiasis control MDA program for children aged 5 years and below. The resources used should also be eco-friendly [41].

None of the studies described the nature of the registers that they used for enrolment. Electronic registers that are embedded in tablets could be used to enrol children into a schistosomiasis treatment programs. The use of electronic information management systems in the MDA program could be extended to storing and analysing the clinical assessments of the children to identify other childhood illnesses that need mass intervention. Tablets can be used for controlling the quality of the medical information about the children that is requested using questionnaires, for managing and monitoring the program’s consumables inventory, and for monitoring and evaluation of the progress and impact of the MDA program. A multinational study conducted in low- and medium-income countries (Ghana, Kenya, India, and Pakistan) reported that the initial cost of purchasing electronic tablets and software licensing costs for healthcare program data management could be high [42]. However, because the tablets could be used multiple times for the same program and also across different programs, the purchase of tablets could be a justifiable investment when taking into account economies of scale and economies of scope in healthcare program implementation cost analysis [42, 43]. The limitations of using electronic tablets could include intermittent electricity supply and Internet coverage in some of the areas where the schistosomiasis control MDA program could be necessary [42, 44]. The use of paper-based registers is most common and carries some hidden costs [42]. When the initial cost of buying and setting up electronic systems for treatment data management is unaffordable, paper-based registers could be used.

The WHO recommends that diagnosis should not be made a requirement for the mass drug administration of praziquantel in schistosomiasis-endemic areas [21]. Diagnosis could however be used for monitoring and evaluation of a schistosomiasis control MDA program. To diagnose schistosomiasis in children aged 5 years old and below for monitoring and evaluating a schistosomiasis control MDA program targeting this age group, urine dipstick to detect haematuria caused by urinary schistosomiasis and the POC-CCA to detect intestinal schistosomiasis could be used. Both these methods have the advantages of being performed at the site of the MDA program and are more sensitive than the microscopy-based methods that are normally used to diagnose schistosomiasis in school-going children [40, 45, 46]. The urinary dipstick and POC-CCA point-of-care tests do not require specialized human resources, in particular laboratory technicians, to carry out the testing. Other methods such as the polymerase chain reaction (PCR) and the FLOTAC technologies require additional specially skilled technicians and equipment such as thermocyclers and centrifuges which cannot be used in field [47].

The activities that are involved in treating schistosomiasis in children aged 5 years and below include taking weight or height measurements, calculating dosage, feeding the children, making PZQ more palatable to the children, and administering the PZQ. Height rather than weight could be used to determine the dose of PZQ to be given to the children [16]. This is because the dose poles that are used to measure height are less expensive to buy and maintain compared to the weight scales that could be used if weight is used to determine the dosage [48]. The extended dose pole addresses the limitation of the exclusion of children shorter than 94 cm from being treated based on the dose pole [16]. The use of electronic health systems management could eliminate the need for dose poles and weight scales by providing data that could be used to perform weight-for-age calculations [49]. The age of the child could then be used to calculate the appropriate PZQ dose to treat the children [49].

We recommend that bread and juice are the most suitable foods to feed the children before treatment. This is because bread and juice are filling and yet easily available in most communities and also require very little labour to prepare [50]. Fortified spreads could be used on the bread to enhance its nutritional value [51]. Juice also has the added capability to sweeten the PZQ making it more palatable for the children [52]. An alternative to bread and juice could be fortified cereal [53]. Fortified cereal has the advantage of providing multi-nutrients to children [53], thereby addressing the needs of the schistosomiasis control MDA program for children aged 5 years old and below, tackling the challenge of malnutrition [54] especially since schistosomiasis and childhood malnutrition often exist as co-epidemics [15, 54]. The studies reported using either pestle and mortar or spoons to crush the PZQ tablets. Ideally, the pestle and mortar could be used. This is because the pestle and mortar are the best tools to use to crush the tablets and are also inexpensive [55]. Spoons are less efficient in crushing tablets but could also be used when pestle and mortar are not available.

Schistosomiasis control MDA programs for children aged 5 years old and below could be carried out in clinics or schools. The use of clinics for such an MDA program is encouraged by the WHO [9]. Schools on the other hand have been successfully used by schistosomiasis control MDA programs to treat SAC [29, 56]. Since some ECD centres are attached to schools, the same operational strategies that have been used to target SAC could be used to target pre-school-going children (PSAC) [29, 33]. Children who are not enrolled in ECD centres could be invited to be part of MDA programs. Faith-based establishments such as churches and mosques are used for healthcare programs in some resource-limited settings [57, 58] and could be used to mobilize people to enrol their children who are aged 5 years and below into schistosomiasis control MDA programs [59, 60]. Faith-based establishments could also be used as treatment sites for the MDA program. The choice between using clinics, ECD centres, crèches, and faith-based establishments depends on the prevailing government policy and on where the children under 5 years who are at risk of schistosomiasis could be best accessed for treatment in the community where the MDA program is required.

The studies we reviewed reported on using a variety of human resources such as paediatricians, medical doctors, nurses, laboratory technicians, and community health workers. Paediatricians, medical doctors, and laboratory technicians are seldom available in resource-limited settings such as those that are affected by schistosomiasis [61]. Nurses could therefore implement the schistosomiasis control MDA program for children aged 5 years old and below. This is because nurses have been found to successfully implement paediatric healthcare interventions at the primary healthcare level in the resource-limited setting where schistosomiasis is mostly found [62]. Community health workers are needed to support the clinicians in MDA programs because of human resources constraints in most areas that are affected by schistosomiasis [63, 64]. Considerations of the disruption of routine curative functions of the nurses in the clinics where the nurses normally work and the remuneration motivation of community caregivers should be taken into account when developing a human resources strategy for the implementation of an MDA program [61, 65] to control schistosomiasis in children aged 5 years and below.

The strength of this study is that the studies are from 5 different countries which makes them generalizable to resource-limited settings in Africa and similar settings globally. The limitations of the study are that we did not perform interviews as recommended by Arksey and O’Malley’s framework for systematic reviews [19]. The interviews could have given us more information on the resources that are applicable for use in schistosomiasis control MDA programs for children under 5 years in different settings. We, however, could not perform these interviews due to challenges in getting authorization from several countries to conduct the interviews within the duration of the study. Another limitation of the review was that the inclusion criterion excluded studies that were not in English because there were no interpreters. The exclusion of studies that were written in other languages besides English could have created bias. The diversity of countries in which studies were done alleviates the impact of the language bias.