Prevalence of schistosomiasis in infants and pre-school-aged children

Several studies of urinary schistosomiasis have tended to focus mainly on school-aged children, with little or no emphasis on pre-school-aged children, and where pre-school-aged children were part of the study, information about them was often subsumed (Akogun and Akogun, Reference Akogun and Akogun1996; Ofoezie et al. Reference Ofoezie, Christensen and Madsen1998). Table 1 summarizes the available studies of schistosomiasis in infant and pre-school-aged children in sub-Saharan Africa. Mafiana et al. (Reference Mafiana, Ekpo and Ojo2003) first reported infection among pre-school-aged children in settlements near Oyan dam, southwestern Nigeria. Out of the 209 pre-school children examined, 150 (71·8%) had an infection with 42·9% of them before their first birthday and 17·7% of the pre-school children had visible haematuria. Over the years, other studies from sub-Saharan Africa have been published. Within Nigeria alone, infections of infants or pre-school-aged children have been reported in several schistosomiasis endemic communities. The following studies are here included: in Adim, Cross River State, 25 of 126 pre-school-aged children examined, 19·8% were infected (Opara et al. Reference Opara, Udoidung and Ukpong2007). In Ilewo-Orile, Ogun State, 97 infections were reported out of 167 pre-chool-aged children (58·1%) examined (Ekpo et al. Reference Ekpo, Akintunde, Oluwole, Sam-Wobo and Mafiana2010) and in Obada/Korede, Ijebu East, Ogun State, 14 infections were reported from 83 pre-school-aged children (16·9%) examined (Ekpo et al. Reference Ekpo, Alabi, Oluwole and Sam-Wobo2011).

Table 1. Summary of prevalence report of schistosomiasis in infants and pre-school-aged children in sub-Saharan Africa

(SEA-ELISA, Soluble Egg Antigen Enzyme-Linked Immunosorbent Assay; CCA, Circulating Cathodic Antigen.)

In Awutu-Efutu Senya district, in the Central region of Ghana, a monoclonal antibody dipstick test detected 33·0% infection from 97 children aged 2 months to 5 years, compared with 11·2% that was detected using urine microscopy (Bosompem et al. Reference Bosompem, Bentum, Otchere, Anyan, Brown, Osada, Takeo, Kojima and Ohta2004). In Falmado and Diambala communities of Niger, the prevalence of S. haematobium infection among pre-school-aged children was 50·5% and 60·5%, respectively (Garba et al. Reference Garba, Barkiré, Djibo, Lamine, Sofo, Gouvras, Bosqué-Oliva, Webster, Stothard, Utzinger and Fenwick2010). Infection with S. mansoni was 43·8% in Diambala. Mixed infection of both S. haematobium and S. mansoni among pre-school-aged children was 28·6% (Garba et al. Reference Garba, Barkiré, Djibo, Lamine, Sofo, Gouvras, Bosqué-Oliva, Webster, Stothard, Utzinger and Fenwick2010). In Sahelian rural communities of Mali, of 338 pre-school-aged children examined, 173 (51·2%) were infected with S. haematobium (Dabo et al. Reference Dabo, Badawi, Bary and Doumbo2011).

In East Africa, prevalence of 86·0% and 25·0% of S. mansoni infection in infants less than 3 years of age were observed in the villages of Bugoto and Bwondha, along the Ugandan shoreline of Lake Victoria (Odogwu et al. Reference Odogwu, Ramamurthy, Kabatereine, Kazibwe, Tukahebwa, Webster, Fenwick and Stothard2006). Similarly, 62·3% prevalence for intestinal schistosomiasis was reported along shore villages of Lakes Albert and Victoria in Uganda (Sousa-Figueiredo et al. Reference Sousa-Figueiredo, Pleasant, Day, Betson, Rollinson, Montresor, Kazibwe, Kabatereine and Stothard2010a). In Kenya, a prevalence of 14·0% was reported among 1-year-old infants out of 216 screened in Usoma community (Verani et al. Reference Verani, Abudho, Montgomery, Mwinzi, Shane, Butler, Karanja and Secor2011). However, on Zanzibar Island, Tanzania, infection with urinary schistosomiasis in infants and pre-school-aged children was rare because of lack of contact with water bodies (Sousa-Figueiredo et al. Reference Sousa-Figueiredo, Basáñez, Mgeni, Khamis, Rollinson and Stothard2008). In Zimbabwe, a prevalence of 21% was recorded from 100 pre-school children during a safety and efficacy study using praziquantel (Mutapi et al. Reference Mutapi, Rujeni, Bourke, Mitchell, Appleby, Nausch, Midzi and Mduluza2011).

These studies point to a growing body of evidence that in many endemic communities, schistosomiasis infection – contrary to previous beliefs – starts in early childhood. The presence of infection, points to the fact that infants and pre-schoolers are also at risk of infection like their older school-aged counterparts. The growing concern here is that infection in infants and pre-school-aged children may persist until the child starts school if left untreated. In preventive chemotherapy control programmes infants and pre-school-aged children are not eligible for treatment until school-aged (Stothard and Gabrielli, Reference Stothard and Gabrielli2007a; Sousa-Figueiredo et al. Reference Sousa-Figueiredo, Pleasant, Day, Betson, Rollinson, Montresor, Kazibwe, Kabatereine and Stothard2010a; Ekpo et al. Reference Ekpo, Alabi, Oluwole and Sam-Wobo2011). In some sub-Saharan African countries endemic for schistosomiasis and where treatment rates are still low or non-existent, early development of childhood morbidity can contribute to the long-term impact of clinical features and severity of infection such as in female genital schistosomiasis (Kjetland et al. Reference Kjetland, Poggensee, Helling-Giese, Richter, Sjaastad, Chitsulo, Kumwenda, Gundersen, Krantz and Feldmeier1996, Reference Kjetland, Ndholovu, Mduluza, Gomo, Gwanzura, Mason, Kurewa, Midzi, Friis and Gundersen2005). Since treatment is restricted to school-aged children, infants and pre-schoolers suffer health inequity (Montresor et al. Reference Montresor, Engels, Chitsulo, Bundy, Brooker and Savioli2001; Stothard and Gabrielli, Reference Stothard and Gabrielli2007a,b; Johansen et al. Reference Johansen, Sacko, Vennervald and Kabatereine2007; Stothard et al. Reference Stothard, Sousa-Figueiredo, Betson, Green, Seto, Garba, Sacko, Mutapi, Vaz Nery, Amin, Mutumba-Nakalembe, Navaratnam, Fenwick, Kabatereine, Gabrielli and Montresor2011a).

Factors associated with exposure of infant and pre-school-aged children to infection

Schistosoma infections are intimately linked to occupational activities in adults and recreational activities among school-aged children. For infants and pre-school-aged children, it becomes difficult to comprehend how children in this age group acquire infection, when they are supposed to stay at home or under strict observation by their mothers and caregivers. Studies on water-contact activities and risk factors for infants and pre-school-aged children are scanty. In many of the studies reported thus far, water-contact activities were investigated through questionnaires and focus discussion groups (FDGs) with guardians and caregivers and with older pre-school-aged children. These studies have pointed to the fact that mothers and caregiver expose their infants to infested water in the absence of other safer sources (Mafiana et al. Reference Mafiana, Ekpo and Ojo2003; Bosompem et al. Reference Bosompem, Bentum, Otchere, Anyan, Brown, Osada, Takeo, Kojima and Ohta2004). Mothers and caregivers have admitted taking their infants and pre-school children to bathe in the stream, while older pre-school children visit the water bodies for washing, fetching of water, bathing and swimming (Ekpo et al. Reference Ekpo, Akintunde, Oluwole, Sam-Wobo and Mafiana2010). In Niger, observation showed that 69·8% of the children accompanied their mothers to schistosomiasis transmission sites before their first birthday and that three-quarters of the mothers used water directly drawn from the schistosome-infested irrigation canals to wash their children (Garba et al. Reference Garba, Barkiré, Djibo, Lamine, Sofo, Gouvras, Bosqué-Oliva, Webster, Stothard, Utzinger and Fenwick2010). In Ghana, 29·2% of infants had direct contact with water bodies used by their mothers for domestic purposes (Bosompem et al. Reference Bosompem, Bentum, Otchere, Anyan, Brown, Osada, Takeo, Kojima and Ohta2004). The general agreement from these studies is that infants are exposed to infection by their mothers and caregivers who take them to water sources, or use infested water to bathe them, while the older pre-school children will visit the water bodies for swimming, washing, bathing and other activities. We are yet to better understand the interaction between paediatric schistosomiasis and other childhood diseases such as malaria and intestinal helminithiasis on the immune system. Little is known about childhood morbidity due to schistosomiasis (Betson et al. 2010). Clearly, more investigations are needed to provide information on these risk factors, co-infection with other pathogens and morbidity of childhood schistosomiasis, in order to develop intervention measures targeted at mothers and their pre-school-aged children.

Inclusive dose pole for treatment of schistosomiasis in infants and pre-school-aged children

The current strategy of controlling schistosomiasis focuses on preventive chemotherapy focussing mainly on school-aged children with a single dose of praziquantel at 40 mg/kg (Hotez et al. Reference Hotez, Raff, Fenwick, Richards and Molyneux2007b). The World Health Organization considers that praziquantel is safe for humans 4 years of age and above even though the manufacturer has not explicitly stated the minimum age. Indeed, the safety of praziquantel and other anti-helmintic drugs in infants and pre-school-aged children remains to be fully characterized (Keiser et al. Reference Keiser, Ingram and Utzinger2011). The correct dosage for treatment can be determined using a dose pole (height) as against body weight in preventive chemotherapy and mass drug administration (Hall et al. Reference Hall, Nokes, Wen, Adjei, Kihamia, Mwanri, Bobrow, de Graft-Johnson and Bundy1999). The dose pole measurement has been validated to provide simple and accurate dosage between 20 and 60 mg/kg (Montresor et al. Reference Montresor, Engels, Chitsulo, Bundy, Brooker and Savioli2001, Reference Montresor, Odermatt, Muth, Iwata, Raja'a, Assis, Zulkifli, Kabatereine, Fenwick, Al-Awaidy, Allen, Engels and Savioli2005). The validity of using height for dosing in the field has been confirmed from a study in a Nigerian community (Idowu et al. Reference Idowu, Mafe, Appelt, Adewale, Adeneye, Akinwale, Manafa and Akande2007). However, the pole precludes infants and pre-school-aged children (<94 cm) from treatment. Recently, a study of the safety of praziquantel treatment in infants and pre-school-aged children in Uganda, recorded various mild reactions such as headaches (3·6%) vomiting (9·4%) diarrhoea (10·9%) and urticaria/rash (8·9%) after the first day of treatment, which ameliorated afterwards with a parasitological cure rate of 100% (Sousa-Figueiredo et al. Reference Sousa-Figueiredo, Pleasant, Day, Betson, Rollinson, Montresor, Kazibwe, Kabatereine and Stothard2010a). The study proposed a dose pole that includes infant and pre-schoolers under the height of 94 cm (Sousa-Figueiredo et al. Reference Sousa-Figueiredo, Pleasant, Day, Betson, Rollinson, Montresor, Kazibwe, Kabatereine and Stothard2010a). The assessment and approval of this modified pole will permit dosing of infants and pre-school-aged children for preventive chemotherapy (Sousa-Figueiredo et al. Reference Sousa-Figueiredo, Day, Betson, Kabatereine and Stothard2010b). Other safety and efficacy studies on infants and pre-school-aged children showed that praziquantel is safe (Mutapi et al. 2001). Nevertheless, the degree of adverse events reported by Sousa-Figueiredo et al. (Reference Sousa-Figueiredo, Pleasant, Day, Betson, Rollinson, Montresor, Kazibwe, Kabatereine and Stothard2010a) needs to be addressed through clinical trials on the safety of praziquantel in infants and pre-school-aged children. Fortunately, a recent trial conducted in Uganda among children aged 1–4 years, showed no serious adverse events for praziquantel treatment alone or in combination with mebendazole (Namwanje et al. Reference Namwanje, Kabatereine and Olsen2011). Clearly, there is a need for more in-depth studies (see Table 2) not only on safety and reduced dosage for infant and pre-school-aged children but, most importantly, pharmacokinetic (PK) studies to determine proper drug formulations, dosages and presentations to infants and pre-school-aged children in the frame of preventive chemotherapy, which we do not know (Keiser et al. Reference Keiser, Ingram and Utzinger2011).

Table 2. Research needs pertaining to schistosomiasis among infants and pre-school-aged children

Screening to include infants and pre-school-aged children for preventive chemotherapy

For infants and pre-school-aged children in sub-Saharan Africa to benefit from preventive chemotherapy, improved diagnostic methods for the screening of this age group is desirable. Several diagnostic methods to detect early childhood infection have been investigated for S. mansoni in Uganda. These include fecal occult blood and fecal calprotectin (Betson et al. Reference Betson, Sousa-Figueiredo, Rowell, Kabatereine and Stothard2010); circulating cathodic antigen (CCA), urine dipstick and stool microscopy (Midzi et al. Reference Midzi, Butterworth, Mduluza, Munyati, Deelder and van Dam2009; Stothard et al. Reference Stothard, Sousa-Figuereido, Betson, Adriko, Arinaitwe, Rowell, Besiyge and Kabatereine2011b). It has been shown that, reliance on egg detection in feces for S. mansoni diagnosis in childhood would exclude infants and pre-school-aged children receiving treatment early enough until 3–4 years later (Stothard et al. Reference Stothard, Sousa-Figuereido, Betson, Adriko, Arinaitwe, Rowell, Besiyge and Kabatereine2011b). For S. haematobium, diagnosis in childhood may require the use of the following methods: presence of microhaematuria detected by reagent strips (Mafe, Reference Mafe1997), macrohaematuria investigated by questionnaires (Red Urine Study Group, 1995; Lengeler et al. Reference Lengeler, Utzinger and Tanner2002), proteinuria detected by reagent strips (Mott et al. Reference Mott, Dixon, Osei-Tutu and England1983) or a combination of both microhaematuria and urine microscopy (Lengeler et al. Reference Lengeler, Mshinda, Morona and de Savigny1993; Robinson et al. Reference Robinson, Picon, Sturrock, Sabasio, Lado, Kolaczinski and Brooker2009; Ugbomoiko et al. Reference Ugbomoiko, Dalumo, Ariza, Bezerra and Heukelbach2009a, Reference Ugbomoiko, Obiezue, Ogunniyi and Ofoezieb; Ekpo et al. Reference Ekpo, Alabi, Oluwole and Sam-Wobo2011).

Health education for mothers and caregivers

It is clear that mothers and caregivers contribute substantially to exposing their young children to Schistosoma infection. Control programmes should not rely only on preventive chemotherapy, but should also include development and utilization of health education messages targeted at mothers and caregivers (Stothard et al. Reference Stothard, Sousa-Figueiredo, Betson, Green, Seto, Garba, Sacko, Mutapi, Vaz Nery, Amin, Mutumba-Nakalembe, Navaratnam, Fenwick, Kabatereine, Gabrielli and Montresor2011a). This should be part of current control programme planning. The health education programme must be participatory to include roles for mothers and caregivers on how to avoid taking their infants and pre-school-aged children to infective water bodies (Ekpo et al. Reference Ekpo, Akintunde, Oluwole, Sam-Wobo and Mafiana2010). The usage of infective water bodies for bathing of infants and pre-school-aged children should be discouraged. The boiling of water to kill cercariae before using it to bath infants should be promoted. In addition, erection of health messages on signposts near water bodies to warn pre-school children of the dangers of schistosomiasis infection is recommended. Finally, it is noteworthy that schistosomiasis control programmes be revised to include strategies for treatment and prevention of infection in infants and pre-school-aged children. This may reduce continuous transmission of the disease in communities alongside treating school-aged and adult members of the population.