Putting the treatment of paediatric schistosomiasis into context

Takafira Mduluza, Francisca Mutapi, Takafira Mduluza, Francisca Mutapi

Abstract

Despite increased international efforts to control schistosomiasis using preventive chemotherapy, several challenges still exist in reaching the target populations. Until recently, preschool-aged children had been excluded from the recommended target population for mass drug administration, i.e. primary school children aged 6-15 years. Our studies and those of others provided the evidence base for the need to treat preschool-aged children that led to recommendations by the World Health Organization to include preschool-aged children in treatment programmes in 2010. The major challenge now lies in the unavailability of a child-size formulation of the appropriate anthelmintic drug, praziquantel.The currently available formulation of praziquantel presents several problems. First, it is a large tablet, making it difficult for young children and infants to swallow it and thus requires its breaking/crushing to allow for safe uptake. Second, it is bitter so it is often mixed with a sweetener to make it palatable for young children. Third, the current formulation of 600 mg does not allow for flexible dose adjustments for this age group. Thus, there is a need to formulate a child-appropriate praziquantel tablet.This paper discusses the target product profile for paediatric praziquantel, as well as knowledge gaps pertinent to the successful control of schistosome infection and disease in preschool-aged children.

Keywords: Child-size medicine; Drug pipeline; Paediatric schistosomiasis; Praziquantel; Target product profile.

Figures

Fig. 1
Fig. 1
While the mother is busy with laundry chores, the child is placed in a dish with water collected from the river, exposing the child to infection if the water contains cercariae. This was observed to be a common practice in the community where children aged below five years were found to harbour the S. haematobium infection

References

    1. Chitsulo LD, Engels D, Montresor A, Savioli L. Global status of schistosomiasis. Acta Trop. 2000;77:41–51. doi: 10.1016/S0001-706X(00)00122-4.
    1. World Health Organization . Prevention and Control of Schistosomiasis and Soil-transmitted Helminthiasis. Geneva: World Health Organization; 2002.
    1. World health Organization . Report of a meeting to review the results of studies on the treatment of schistosomiasis in pre-school-age children. Geneva: World Health Organization; 2012.
    1. Webster BL, Southgate VR, Littlewood DTL. A revision of the interrelationships of Schistosoma including the recently described Schistosoma guineensis. Int J Parasitol. 2006;36:947–955. doi: 10.1016/j.ijpara.2006.03.005.
    1. Gryseels B, Polman K, Clerinx J, Kestens L. Human Schistosomiasis. Lancet. 2006;368:1039–1126. doi: 10.1016/S0140-6736(06)69440-3.
    1. van der Werf MJ, de Vlas SJ, Brooker S, Looman CW, Nagelkerke NJ, Habbema JD, Engels D. Quantification of clinical morbidity associated with schistosome infection in sub- Saharan Africa. Acta Trop. 2003;86:125–139. doi: 10.1016/S0001-706X(03)00029-9.
    1. World Health Organisation . WHO technical Report Series. Geneva: World Health Organisation; 2002. Prevention and control of schistosomiasis and soil-transmisted helminthiasis.
    1. Ndhlovu PD, Mduluza T, Kjetland EF, Midzi N, Nyanga L, Gundersen SG, Friis H, Gomo E. Prevalence of urinary schistosomiasis and HIV in females living in a rural community of Zimbabwe: does age matter? Trans R Soc Trop Med Hyg. 2007;101(5):433–8. doi: 10.1016/j.trstmh.2006.08.008.
    1. Walker M, Mabud TS, Olliaro PL, Coulibaly JT, King CH, Raso G, et al. New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel. Parasit Vectors. 2016;9:41. doi: 10.1186/s13071-016-1312-0.
    1. Chen MG. Assessment of morbidity due to Schistosoma japonicum infection in China. Infect Dis Poverty. 2014;3(1):6. doi: 10.1186/2049-9957-3-6.
    1. Wami WM, Nausch N, Midzi N, Gwisai R, Mduluza T, Woolhouse M, et al. Identifying and evaluating field indicators of urogenital schistosomiasis-related morbidity in preschool-aged children. PLoS Negl Trop Dis. 2015;9(3):e0003649. doi: 10.1371/journal.pntd.0003649.
    1. Colley DG, Bustinduy AL, Secor WE, King CH. Human schistosomiasis. Lancet. 2014;383(9936):2253–64. doi: 10.1016/S0140-6736(13)61949-2.
    1. Garba A, Barkiré N, Djibo A, Lamine MS, Sofo B, Gouvras AN, et al. Schistosomiasis in infants and preschool-aged children: Infection in a single Schistosoma haematobium and a mixed S. haematobium- S. mansoni foci of Niger. Acta Trop. 2010;115(3):212–9. doi: 10.1016/j.actatropica.2010.03.005.
    1. Mafiana CF, Ekpo UF, Ojo DA. Urinary schistosomiasis in preschool children in settlements around Oyan Reservoir in Ogun State, Nigeria: implications for control. Trop Med Int Health. 2003;8:78–82. doi: 10.1046/j.1365-3156.2003.00988.x.
    1. Ekpo UF, Laja-Deile A, Oluwole AS, Sam-Wobo SO, Mafiana CF. Urinary schistosomiasis among preschool children in a rural community near Abeokuta. Nigeria Parasit Vectors. 2010;3:58. doi: 10.1186/1756-3305-3-58.
    1. Mutapi F, Rujeni N, Bourke C, Mitchell K, Appleby L, Nausch N, Midzi N, Mduluza T. Schistosoma haematobium treatment in 1–5 year old children: safety and efficacy of the antihelminthic drug praziquantel. PLoS Negl Trop Dis. 2011;5(5):e1143. doi: 10.1371/journal.pntd.0001143.
    1. Sousa-Figueiredo JC, Basanez MG, Mgeni AF, Khamis IS, Rollinson D, Stothard JR. A parasitological survey, in rural Zanzibar, of pre-school children and their mothers for urinary schistosomiasis, soil-transmitted helminthiases and malaria, with observations on the prevalence of anaemia. Ann Trop Med Parasitol. 2008;102:679–92. doi: 10.1179/136485908X337607.
    1. Uneke JC, Egede MU. Impact of urinary schistosomiasis on nutritional status of school children in south-eastern Nigeria. Internet J Health. 2009;9(1):11.
    1. Poole H, Terlouw DJ, Naunje A, Mzembe K, Stanton M, Betson M, et al. Schistosomiasis in pre-school-age children and their mothers in Chikhwawa district Malawi with notes on characterization of schistosomes and snails. Parasit Vectors. 2014;7:153. doi: 10.1186/1756-3305-7-153.
    1. Meurs L, Mbow M, Vereecken K, Menten J, Mboup S, Polman K. Bladder morbidity and hepatic fibrosis in mixed Schistosoma haematobium and S. mansoni infections: A population-wide study in Northern Senegal. PLoS Negl Trop Dis. 2012;6(9):e1829. doi:10.1371/journal.pntd.0001829.
    1. Olliaro PL, Vaillant MT, Belizario VJ, Lwambo NJ, Ouldabdallahi M, Pieri OS, et al. A multicentre randomized controlled trial of the efficacy and safety of single-dose praziquantel at 40 mg/kg vs. 60 mg/kg for treating intestinal schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil. PLoS Negl Trop Dis. 2011;5(6):e1165. doi: 10.1371/journal.pntd.0001165.
    1. Stothard JR, Sousa-Figueiredo JC, Betson M, Green HK, Seto EY, Garba A, et al. Closing the praziquantel treatment gap: new steps in epidemiological monitoring and control of schistosomiasis in African infants and preschool-aged children. Parasitology. 2011;138:1593–606. doi: 10.1017/S0031182011001235.
    1. Odogwu SE, Ramamurthy NK, Kabatereine NB, Kazibwe F, Tukahebwa E, Webster JP, Fenwick A, Stothard JR. Schistosoma mansoni in infants (aged < 3 years) along the Ugandan shoreline of Lake Victoria. Ann Trop Med Parasitol. 2006;100:315–326. doi: 10.1179/136485906X105552.
    1. Bustinduy AL, Friedman JF, Kjetland EF, et al. Expanding praziquantel (pzq) access beyond mass drug administration programs: paving a way forward for a pediatric pzq formulation for schistosomiasis. PLoS Negl Trop Dis. 2016;10(9):e0004946. doi: 10.1371/journal.pntd.0004946.
    1. Fenwick A, Savioli L, Engels D, Robert Bergquist N, Todd MH. Drugs for the control of parasitic diseases: current status and development in schistosomiasis. Trends Parasitol. 2003;19(11):509–15. doi: 10.1016/j.pt.2003.09.005.
    1. Sousa-Figueiredo JC, Betson M, Atuhaire A, Arinaitwe M, Navaratnam AM, Kabatereine NB, Bickle Q, Stothard JR. Performance and safety of praziquantel for treatment of intestinal schistosomiasis in infants and preschool children. PLoS Negl Trop Dis. 2012;6:e1864. doi: 10.1371/journal.pntd.0001864.
    1. Malhorta I, Mungai P, Wamachi A, Kioko J, Ouma JH, Kazura JW, King CL. Helminth and Bacillus Calmette-Guerin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. J Immunol. 1999;162(11):6843–8.
    1. World Health Oganization . Report of a meeting to review the results of studies on the treatment of schistosomiasis in preschool-age children. Geneva: World Health Oganization; 2010.
    1. Meyer T, Sekljic H, Fuchs S, Bothe H, Schollmeyer D, Miculka C. Taste, a new incentive to switch to (r)-praziquantel in schistosomiasis treatment. PLoS Negl Trop Dis. 2009;3(1):e357. doi: 10.1371/journal.pntd.0000357.
    1. Bustinduy AL, Waterhouse D, de Sousa-Figueiredo JC, Roberts SA, Atuhaire A, Van Dam GJ et al. Population pharmacokinetics and pharmacodynamics of praziquantel in Ugandan children with intestinal schistosomiasis: Higher dosages are required for maximal efficacy. MBio. 2016;7(4). doi: 10.1128/mBio.00227-16.
    1. Warnich L, Drogemoller BI, Pepper MS, Dandara C, Wright GEB. Pharmacogenomics research in South Africa: Lessons learned and future opportunities in the Rainbow Nation. Curr Pharmacogenomics Person Med. 2011;9(3):191–207. doi: 10.2174/187569211796957575.
    1. Bataller R, North KE, Brenner DA. Genetic polymorphisms and the progression of liver fibrosis: a critical appraisal. Hepatology. 2003;37:493–503. doi: 10.1053/jhep.2003.50127.
    1. Bethony JM, Quinnell RJ. Genetic epidemiology of human schistosomiasis in Brazil. Acta Trop. 2008;108(2–3):166–74. doi: 10.1016/j.actatropica.2007.11.008.
    1. Lubomirov R, Colombo S, di Iulio J, Ledergerber B, Martinez R, Cavassini M, Hirschel B, et al. Association of pharmacogenetics markers with premature discontinuation of first line anti-HIV therapy: An observational cohort study. J Infect Dis. 2011;203(2):246–57. doi: 10.1093/infdis/jiq043.
    1. Pang T. Pharmacogenomics and personalized medicine for the developing world - too soon or just-in-time? a personal view from the world health organization. Curr Pharmacogenomics Person Med. 2009;7(3):149–157. doi: 10.2174/1875692110907030149.
    1. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747–53. doi: 10.1038/nature08494.
    1. Ashley EA, Butte AJ, Wheeler MT, Chen R, Klein TE, Dewey FE, et al. Clinical assessment incorporating a personal genome. Lancet. 2010;375(9725):1525–35. doi: 10.1016/S0140-6736(10)60452-7.
    1. Motsinger-Reif A, Jorgenson E, Relling MV, Kroetz DL, Weinshilboum R, Cox NJ, Roden DM. Genome-wide association studies in pharmacogenomics: successes and lessons. Pharmacogenet Genomics. 2013;23(8):383–94. doi: 10.1097/FPC.0b013e32833d7b45.
    1. Wester K, Jönsson AK, Spigset O, Druid H, Hägg S. Incidence of fatal adverse drug reactions: a population based study. Br J Clin Pharmacol. 2008;65:573–579. doi: 10.1111/j.1365-2125.2007.03064.x.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera