Treatment of pre-school children under 6 years of age for schistosomiasis: safety, efficacy and acceptability of praziquantel
Keywords:
Schistosomiasis, Praziquantel,, Safety, Young Children.
Abstract
Background
The World Health Organization (WHO) recommends praziquantel for the control and treatment of
schistosomiasis, with no real alternative. Pre-school children are excluded from population
treatment programs mainly due to paucity of safety data on this age group.
Objectives: This study investigated safety, efficacy and acceptability of praziquantel for the
treatment of S. haematobium and S. mansoni infections among pre-school children aged <6years.
The study also investigated the burden of schistosomiasis in this age group.
Methods: Pre-school children (n=188) from Sudan were included in the study. The children were
treated with praziquantel tablets at a single dose of 40 mg/kg body weight. Adverse events were
assessed at 24 hours and 7 days later, via questionnaire administration to parents and guardians.
Efficacy of treatment was assessed at 1, 3 and 6 months by examining stool and urine samples for
schistosome eggs. Acceptability was determined by the number of children spitting or vomiting
during administration of the drug.
Results: The burden of schistosomiasis among pre-school children aged <6 years was high
(31.1%), and this was comparable to that observed among school children-aged 6 years (32%).
Praziquantel treatment achieved high cure rates (egg negative) for both S. haematobium and S.
mansoni infections when assessed at 1 month after treatment (89.6-92.1%) and remained high for S.
haematobium (89.6-100%) up to 6 months. However, cure rate dropped from 90.5% at one month
to 58.8% and 69.2% at 3 and 6 months among S. mansoni-treated children. Praziquantel treatment
decreased egg counts considerably with post-treatment geometric mean egg reductions rates ranging
from 96.4% to 99.4% at 1 month. Acceptability of praziquantel treatment was high, only for one
child the dose had to be repeated after initial spitting. Treatment resolved haematuria and improved
weight of the children. There were no drug-related adverse events in all the treated children during
follow-up at 24 hours and 7 days.
Conclusions: Praziquantel is safe, effective and acceptable among children aged <6 years. Preschool
children represent a high risk group for schistosomiasis and should be included in population
treatment programs.
References
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13. Doehring-Schwerdtfeger E, Abdel-Rahim IM,Kardorff R et al. Ultrasonographical investigationof periportal fibrosis in children with Schistosomamansoni infection: reversibility of morbiditytwenty-three months after treatment withpraziquantel. The American journal of tropicalmedicine and hygiene. 1992;46(4):409.
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17. Doenhoff MJ, Cioli D, Utzinger J. Praziquantel:mechanisms of action, resistance and newderivatives for schistosomiasis. Current opinion ininfectious diseases. 2008;21(6):659-67.
18. Danso-Appiah A, De Vlas SJ. Interpreting lowpraziquantel cure rates of Schistosoma mansoniinfections in Senegal. Trends in parasitology.2002;18(3):125-9.
19. Fenwick A. Waterborne infectious diseases—could they be consigned to history? Science.2006;313(5790):1077-81.
20. Stothard JR, Gabrielli AF. Schistosomiasis inAfrican infants and preschool children: to treat ornot to treat? Trends in parasitology.2007;23(3):83-6.
21. Keiser J, Ingram K, Utzinger J. Antiparasiticdrugs for paediatrics: systematic review,formulations, pharmacokinetics, safety, efficacyand implications for control. Parasitology.2011;138:1620-32.
22. World Health Organization. Preventive
chemotherpy in Human HelmenthiasisCoordinated use of Anthelmenthic Drugs inHuman Intervention: a Mannual for HealthProfessionals and Programme Managers. Geneva,World Health Organization; 2006 Contract No.:Document Number|.
23. El Gadal AA. The Blue Nile Health Project: acomprehensive approach to the prevention andcontrol of water associated diseases in irrigateschemes of the Sudan. Journal of TropicalMedicine and Hygiene. 1985;88:57-63.
24. National Ministry of Health. Annual HealthStatistical Report. Sudan: National HealthInformation Centre; 2009 Contract No.: DocumentNumber|.
25. Fenwick A, Cheesmond AK, Amin MA. The roleof field irrigation canals in the transmission ofSchistosoma mansoni in the Gezira Scheme,Sudan. Bulletin of the World Health Organization.1981;59(5):777-86.
26. Katz N, Chaves A, Pellegrino J. A simple devicefor quantitative stool thick-smear technique inschistosomiasis mansoni. Rev Inst Med Trop SaoPaulo. 1972;14(6):397-400.
27. Ageel ARM, Amin MA. Integration ofschistosomiasis control activities into the primaryhealth care system in the Gizan region, SaudArabia. Annals of tropical medicine andparasitology. 1997;91(8):907-16.
28. Bosompem KM, Bentum IA, Otchere J et al.Infant schistosomiasis in Ghana: a survey in anirrigation community. Tropical Medicine International Health. 2004;9(8):917-22.
29. Ekpo UF, Laja-Deile A, Oluwole AS et al. Urinaryschistosomiasis among preschool children in arural community near Abeokuta, Nigeria. Parasites& Vectors. 2010;3(1):58-62.
30. Garba A, Barkiré N, Djibo A et al. Schistosomiasisin infants and preschool-aged children: Infectionin a single Schistosoma haematobium and a mixedS. haematobium-S. mansoni foci of Niger. ActaTropica. 2010;115(3):212-9.
31. Dabo A, Badawi HM, Bary B et al. Urinaryschistosomiasis among preschool-aged children inSahelian rural communities in Mali. Parasites &Vectors. 2011;4:21.
32. Odogwu SE, Ramamurthy NK, Kabatereine NB etal. Schistosoma mansoni in infants (aged< 3 years)along the Ugandan shoreline of Lake Victoria.Annals of tropical medicine and parasitology.2006;100(4):315-26.
33. Sousa-Figueiredo JC, Pleasant J, Day M et al.Treatment of intestinal schistosomiasis in Ugandanpreschool children: best diagnosis, treatmentefficacy and side-effects, and an extendedpraziquantel dosing pole. International Health.2010;2(2):103-13.
34. Amin MA, Fenwick A, Teesdale CH et al. Theassessment of a large snail control programmeover three-year period in the Gezira Irrigated Areaof the Sudan. Annals of tropical medicine andparasitology. 1982;76(4):415.
35. Jukes MC, Nokes CA, Alcock KJ et al. Heavyschistosomiasis associated with poor short-termmemory and slower reaction times in Tanzanianschoolchildren. Trop Med Int Health.2002;7(2):104-17.
36. Hotez PJ, Brindley PJ, Bethony JM et al.Helminth infections: the great neglected tropicaldiseases. The Journal of clinical investigation.2008;118(4):1311-21.
37. Wang L, Utzinger Jr, Zhou X-N. Schistosomiasiscontrol: experiences and lessons from China. TheLancet. 2008;372(9652):1793-5.
38. Danso Appiah A, De Vlas SJ, Bosompem KM etal. Determinants of health seeking behaviour forschistosomiasis related symptoms in the context ointegrating schistosomiasis control within theregular health services in Ghana. TropicalMedicine & International Health. 2004;9(7):784-94.
39. van der Werf MJ, Bosompem KM, de Vlas SJ.Schistosomiasis control in Ghana: casemanagement and means for diagnosis andtreatment within the health system. Transactions ofthe Royal Society of Tropical Medicine andHygiene. 2003;97(2):146-52.
40. Fenwick A, Webster JP, Bosque-Oliva E et al. TheSchistosomiasis Control Initiative (SCI): rationale,development and implementation from 2002–2008. Parasitology. 2009;136(13):1719-30.
41. Danso-Appiah A, Stolk WA, Bosompem KM et al.Health Seeking Behaviour and Utilization of42. Health Facilities for Schistosomiasis-RelatedSymptoms in Ghana. PLoS neglected tropicaldiseases. 2010;4(11):e867.
43. Stothard JR, Sousa-Figueiredo JC, Betson M et al.Closing the praziquantel treatment gap: new stepsin epidemiological monitoring and control ofschistosomiasis in African infants and preschoolagedchildren. Parasitology. 2011;138(12):1593-606.
44. Sabah AA, Fletcher C, Webbe G et al.Schistosoma mansoni: chemotherapy of infections
of different ages. Experimental parasitology.1986;61(3):294-303.
45. Danso-Appiah A, Utzinger J, Liu J et al. Drugsfor treating urinary schistosomiasis. CochraneDatabase Syst Rev. 2008;16(3):CD000053.
46. Mutapi F, Rujeni N, Bourke C et al. Schistosomahaematobium Treatment in 1–5 Year OldChildren: Safety and Efficacy of theAntihelminthic Drug Praziquantel. PLoS neglectedtropical diseases. 2011;5(5):e1143.
47. Cioli D, Pica-Mattoccia L, Archer S.Antischistosomal drugs: past, present... and future?Pharmacology & therapeutics. 1995;68(1):35-85.
48. Utzinger J, Keiser J. Schistosomiasis and soiltransmittedhelminthiasis: common drugs fortreatment and control. Expert
2. Chitsulo L, Engels D, Montresor A et al. Theglobal status of schistosomiasis and its control.Acta Tropica. 2000;77(1):41-51.
3. Hotez PJ, Kamath A. Neglected tropical diseasesin sub-Saharan Africa: review of their prevalence,distribution, and disease burden. PLoS neglectedtropical diseases. 2009;3(8):e412.
4. World Health Organization. Prevention andcontrol of schistosomiasis and soil-transmittedhelminthiasis: report. WHO Techenical ReportSeries No912, Geneva; 2002 Contract No.:Document Number|.
5. Partnership for Child Development. The cost oflarge-scale school health programmes whichdeliver anthelmintics to children in Ghana andTanzania. Acta Tropica. 1999;73(2):183-204.
6. Awasthi S, Bundy DAP, Savioli L. Helminthicinfections. Bmj. 2003;327(7412):431.
7. Zhang Y, Koukounari A, Kabatereine N et al.Parasitological impact of 2-year preventivechemotherapy on schistosomiasis and soiltransmittedhelminthiasis in Uganda. BMCmedicine. 2007;5(1):27.
8. Webster JP, Koukounari A, Lamberton PHL et al.Evaluation and application of potentialschistosome-associated morbidity markers withinlarge-scale mass chemotherapy programmes.Parasitology. 2009;136(13):1789-99.
9. Utzinger J, Raso G, Brooker S et al.Schistosomiasis and neglected tropical diseases:towards integrated and sustainable control and aword of caution. Parasitology. 2009;136(13):1859-74.
10. Savioli L, Albonico M, Engels D et al. Progress inthe prevention and control of schistosomiasis andsoil-transmitted helminthiasis. ParasitologyInternational. 2004;53(2):103-13.
11. Koukounari A, Donnelly C, Sacko M et al. Theimpact of single versus mixed schistosome speciesinfections on liver, spleen and bladder morbiditywithin Malian children pre-and post-praziquanteltreatment. BMC infectious diseases.2010;10(1):227.
12. Hatz CFR. The use of ultrasound inschistosomiasis. Advances in parasitology.2001;48:225-84.
13. Doehring-Schwerdtfeger E, Abdel-Rahim IM,Kardorff R et al. Ultrasonographical investigationof periportal fibrosis in children with Schistosomamansoni infection: reversibility of morbiditytwenty-three months after treatment withpraziquantel. The American journal of tropicalmedicine and hygiene. 1992;46(4):409.
14. World Health Organization. The control ofschistosomiasis and soil-transmitted helminthiasis:report. WHO Techenical Report series No728,Geneva. World Health Organization; 1985.
15. Magnussen P, Ndawi B, Sheshe AK et al. Theimpact of a school health programme on theprevalence and morbidity of urinaryschistosomiasis in Mwera Division, PanganiDistrict, Tanzania. Transactions of the RoyalSociety of Tropical Medicine and Hygiene.2001;95(1):58-64.
16. Fenwick A, Savioli L, Engels D et al. Drugs forthe control of parasitic diseases: current status anddevelopment in schistosomiasis. Trends inparasitology. 2003;19(11):509-15.
17. Doenhoff MJ, Cioli D, Utzinger J. Praziquantel:mechanisms of action, resistance and newderivatives for schistosomiasis. Current opinion ininfectious diseases. 2008;21(6):659-67.
18. Danso-Appiah A, De Vlas SJ. Interpreting lowpraziquantel cure rates of Schistosoma mansoniinfections in Senegal. Trends in parasitology.2002;18(3):125-9.
19. Fenwick A. Waterborne infectious diseases—could they be consigned to history? Science.2006;313(5790):1077-81.
20. Stothard JR, Gabrielli AF. Schistosomiasis inAfrican infants and preschool children: to treat ornot to treat? Trends in parasitology.2007;23(3):83-6.
21. Keiser J, Ingram K, Utzinger J. Antiparasiticdrugs for paediatrics: systematic review,formulations, pharmacokinetics, safety, efficacyand implications for control. Parasitology.2011;138:1620-32.
22. World Health Organization. Preventive
chemotherpy in Human HelmenthiasisCoordinated use of Anthelmenthic Drugs inHuman Intervention: a Mannual for HealthProfessionals and Programme Managers. Geneva,World Health Organization; 2006 Contract No.:Document Number|.
23. El Gadal AA. The Blue Nile Health Project: acomprehensive approach to the prevention andcontrol of water associated diseases in irrigateschemes of the Sudan. Journal of TropicalMedicine and Hygiene. 1985;88:57-63.
24. National Ministry of Health. Annual HealthStatistical Report. Sudan: National HealthInformation Centre; 2009 Contract No.: DocumentNumber|.
25. Fenwick A, Cheesmond AK, Amin MA. The roleof field irrigation canals in the transmission ofSchistosoma mansoni in the Gezira Scheme,Sudan. Bulletin of the World Health Organization.1981;59(5):777-86.
26. Katz N, Chaves A, Pellegrino J. A simple devicefor quantitative stool thick-smear technique inschistosomiasis mansoni. Rev Inst Med Trop SaoPaulo. 1972;14(6):397-400.
27. Ageel ARM, Amin MA. Integration ofschistosomiasis control activities into the primaryhealth care system in the Gizan region, SaudArabia. Annals of tropical medicine andparasitology. 1997;91(8):907-16.
28. Bosompem KM, Bentum IA, Otchere J et al.Infant schistosomiasis in Ghana: a survey in anirrigation community. Tropical Medicine International Health. 2004;9(8):917-22.
29. Ekpo UF, Laja-Deile A, Oluwole AS et al. Urinaryschistosomiasis among preschool children in arural community near Abeokuta, Nigeria. Parasites& Vectors. 2010;3(1):58-62.
30. Garba A, Barkiré N, Djibo A et al. Schistosomiasisin infants and preschool-aged children: Infectionin a single Schistosoma haematobium and a mixedS. haematobium-S. mansoni foci of Niger. ActaTropica. 2010;115(3):212-9.
31. Dabo A, Badawi HM, Bary B et al. Urinaryschistosomiasis among preschool-aged children inSahelian rural communities in Mali. Parasites &Vectors. 2011;4:21.
32. Odogwu SE, Ramamurthy NK, Kabatereine NB etal. Schistosoma mansoni in infants (aged< 3 years)along the Ugandan shoreline of Lake Victoria.Annals of tropical medicine and parasitology.2006;100(4):315-26.
33. Sousa-Figueiredo JC, Pleasant J, Day M et al.Treatment of intestinal schistosomiasis in Ugandanpreschool children: best diagnosis, treatmentefficacy and side-effects, and an extendedpraziquantel dosing pole. International Health.2010;2(2):103-13.
34. Amin MA, Fenwick A, Teesdale CH et al. Theassessment of a large snail control programmeover three-year period in the Gezira Irrigated Areaof the Sudan. Annals of tropical medicine andparasitology. 1982;76(4):415.
35. Jukes MC, Nokes CA, Alcock KJ et al. Heavyschistosomiasis associated with poor short-termmemory and slower reaction times in Tanzanianschoolchildren. Trop Med Int Health.2002;7(2):104-17.
36. Hotez PJ, Brindley PJ, Bethony JM et al.Helminth infections: the great neglected tropicaldiseases. The Journal of clinical investigation.2008;118(4):1311-21.
37. Wang L, Utzinger Jr, Zhou X-N. Schistosomiasiscontrol: experiences and lessons from China. TheLancet. 2008;372(9652):1793-5.
38. Danso Appiah A, De Vlas SJ, Bosompem KM etal. Determinants of health seeking behaviour forschistosomiasis related symptoms in the context ointegrating schistosomiasis control within theregular health services in Ghana. TropicalMedicine & International Health. 2004;9(7):784-94.
39. van der Werf MJ, Bosompem KM, de Vlas SJ.Schistosomiasis control in Ghana: casemanagement and means for diagnosis andtreatment within the health system. Transactions ofthe Royal Society of Tropical Medicine andHygiene. 2003;97(2):146-52.
40. Fenwick A, Webster JP, Bosque-Oliva E et al. TheSchistosomiasis Control Initiative (SCI): rationale,development and implementation from 2002–2008. Parasitology. 2009;136(13):1719-30.
41. Danso-Appiah A, Stolk WA, Bosompem KM et al.Health Seeking Behaviour and Utilization of42. Health Facilities for Schistosomiasis-RelatedSymptoms in Ghana. PLoS neglected tropicaldiseases. 2010;4(11):e867.
43. Stothard JR, Sousa-Figueiredo JC, Betson M et al.Closing the praziquantel treatment gap: new stepsin epidemiological monitoring and control ofschistosomiasis in African infants and preschoolagedchildren. Parasitology. 2011;138(12):1593-606.
44. Sabah AA, Fletcher C, Webbe G et al.Schistosoma mansoni: chemotherapy of infections
of different ages. Experimental parasitology.1986;61(3):294-303.
45. Danso-Appiah A, Utzinger J, Liu J et al. Drugsfor treating urinary schistosomiasis. CochraneDatabase Syst Rev. 2008;16(3):CD000053.
46. Mutapi F, Rujeni N, Bourke C et al. Schistosomahaematobium Treatment in 1–5 Year OldChildren: Safety and Efficacy of theAntihelminthic Drug Praziquantel. PLoS neglectedtropical diseases. 2011;5(5):e1143.
47. Cioli D, Pica-Mattoccia L, Archer S.Antischistosomal drugs: past, present... and future?Pharmacology & therapeutics. 1995;68(1):35-85.
48. Utzinger J, Keiser J. Schistosomiasis and soiltransmittedhelminthiasis: common drugs fortreatment and control. Expert
