Efficacy of single versus four repeated doses of praziquantel against Schistosoma mansoni infection in school-aged children from Côte d'Ivoire based on Kato-Katz and POC-CCA: An open-label, randomised controlled trial (RePST).
Adolescent
Animals
Anthelmintics
/ administration & dosage
Antigens, Helminth
/ urine
Chemoprevention
/ methods
Child
Child, Preschool
Cote d'Ivoire
Drug Monitoring
/ methods
Female
Glycoproteins
/ urine
Helminth Proteins
/ urine
Humans
Male
Parasitology
/ methods
Praziquantel
/ administration & dosage
Schistosoma mansoni
/ isolation & purification
Schistosomiasis mansoni
/ drug therapy
Schools
Treatment Outcome
Urine
/ parasitology
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
13
12
2019
accepted:
02
03
2020
revised:
01
04
2020
pubmed:
21
3
2020
medline:
14
5
2020
entrez:
21
3
2020
Statut:
epublish
Résumé
Preventive chemotherapy with praziquantel (PZQ) is the cornerstone of schistosomiasis control. However, a single dose of PZQ (40 mg/kg) does not cure all infections. Repeated doses of PZQ at short intervals might increase efficacy in terms of cure rate (CR) and intensity reduction rate (IRR). Here, we determined the efficacy of a single versus four repeated treatments with PZQ on Schistosoma mansoni infection in school-aged children from Côte d'Ivoire, using two different diagnostic tests. An open-label, randomized controlled trial was conducted from October 2018 to January 2019. School-aged children with a confirmed S. mansoni infection based on Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) urine cassette test were randomly assigned to receive either a single or four repeated doses of PZQ, administered at two-week intervals. The primary outcome was the difference in CR between the two treatment arms, measured by triplicate KK thick smears 10 weeks after the first treatment. Secondary outcomes included CR estimated by POC-CCA, IRR by KK and POC-CCA, and safety of repeated PZQ administration. During baseline screening, 1,022 children were assessed for eligibility of whom 153 (15%) had a detectable S. mansoni infection, and hence, were randomized to the standard treatment group (N = 70) and the intense treatment group (N = 83). Based on KK, the CR was 42% (95% confidence interval (CI) 31-52%) in the standard treatment group and 86% (95% CI 75-92%) in the intense treatment group. Observed IRR was 72% (95% CI 55-83%) in the standard treatment group and 95% (95% CI 85-98%) in the intense treatment group. The CR estimated by POC-CCA was 18% (95% CI 11-27%) and 36% (95% CI 26-46%) in the standard and intense treatment group, respectively. Repeated PZQ treatment did not result in a higher number of adverse events. The observed CR using KK was significantly higher after four repeated treatments compared to a single treatment, without an increase in adverse events. Using POC-CCA, the observed CR was significantly lower than measured by KK, indicating that PZQ may be considerably less efficacious as concluded by KK. Our findings highlight the need for reliable and more accurate diagnostic tools, which are essential for monitoring treatment efficacy, identifying changes in transmission, and accurately quantifying the intensity of infection in distinct populations. In addition, the higher CR in the intense treatment group suggests that more focused and intense PZQ treatment can help to advance schistosomiasis control. www.clinicaltrials.gov NCT02868385.
Sections du résumé
BACKGROUND
Preventive chemotherapy with praziquantel (PZQ) is the cornerstone of schistosomiasis control. However, a single dose of PZQ (40 mg/kg) does not cure all infections. Repeated doses of PZQ at short intervals might increase efficacy in terms of cure rate (CR) and intensity reduction rate (IRR). Here, we determined the efficacy of a single versus four repeated treatments with PZQ on Schistosoma mansoni infection in school-aged children from Côte d'Ivoire, using two different diagnostic tests.
METHODS
An open-label, randomized controlled trial was conducted from October 2018 to January 2019. School-aged children with a confirmed S. mansoni infection based on Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) urine cassette test were randomly assigned to receive either a single or four repeated doses of PZQ, administered at two-week intervals. The primary outcome was the difference in CR between the two treatment arms, measured by triplicate KK thick smears 10 weeks after the first treatment. Secondary outcomes included CR estimated by POC-CCA, IRR by KK and POC-CCA, and safety of repeated PZQ administration.
PRINCIPAL FINDINGS
During baseline screening, 1,022 children were assessed for eligibility of whom 153 (15%) had a detectable S. mansoni infection, and hence, were randomized to the standard treatment group (N = 70) and the intense treatment group (N = 83). Based on KK, the CR was 42% (95% confidence interval (CI) 31-52%) in the standard treatment group and 86% (95% CI 75-92%) in the intense treatment group. Observed IRR was 72% (95% CI 55-83%) in the standard treatment group and 95% (95% CI 85-98%) in the intense treatment group. The CR estimated by POC-CCA was 18% (95% CI 11-27%) and 36% (95% CI 26-46%) in the standard and intense treatment group, respectively. Repeated PZQ treatment did not result in a higher number of adverse events.
CONCLUSION/SIGNIFICANCE
The observed CR using KK was significantly higher after four repeated treatments compared to a single treatment, without an increase in adverse events. Using POC-CCA, the observed CR was significantly lower than measured by KK, indicating that PZQ may be considerably less efficacious as concluded by KK. Our findings highlight the need for reliable and more accurate diagnostic tools, which are essential for monitoring treatment efficacy, identifying changes in transmission, and accurately quantifying the intensity of infection in distinct populations. In addition, the higher CR in the intense treatment group suggests that more focused and intense PZQ treatment can help to advance schistosomiasis control.
TRIAL REGISTRATION
www.clinicaltrials.gov NCT02868385.
Identifiants
pubmed: 32196506
doi: 10.1371/journal.pntd.0008189
pii: PNTD-D-19-02069
pmc: PMC7112237
doi:
Substances chimiques
Anthelmintics
0
Antigens, Helminth
0
CCA protein, Schistosoma mansoni
0
Glycoproteins
0
Helminth Proteins
0
Praziquantel
6490C9U457
Banques de données
ClinicalTrials.gov
['NCT02868385']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0008189Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Clin Microbiol Infect. 2015 Jun;21(6):529-42
pubmed: 25843503
PLoS Negl Trop Dis. 2017 Nov 13;11(11):e0006054
pubmed: 29131820
PLoS Comput Biol. 2013;9(12):e1003402
pubmed: 24367250
PLoS Negl Trop Dis. 2011 Sep;5(9):e1321
pubmed: 21949893
PLoS Negl Trop Dis. 2015 May 26;9(5):e0003796
pubmed: 26011733
PLoS Negl Trop Dis. 2014 Jul 24;8(7):e2865
pubmed: 25058013
Parasit Vectors. 2017 Jan 26;10(1):47
pubmed: 28126024
Lancet. 2005 Apr 30-May 6;365(9470):1561-9
pubmed: 15866310
Clin Infect Dis. 2010 May 1;50(9):1205-13
pubmed: 20350194
Trop Med Int Health. 2001 Oct;6(10):817-25
pubmed: 11679130
PLoS Negl Trop Dis. 2018 Jun 28;12(6):e0006484
pubmed: 29953454
J Biomed Inform. 2009 Apr;42(2):377-81
pubmed: 18929686
PLoS Negl Trop Dis. 2015 Jun 18;9(6):e0003821
pubmed: 26086551
Parasit Vectors. 2016 Jan 27;9:41
pubmed: 26813154
Trends Parasitol. 2014 Nov;30(11):528-37
pubmed: 25217844
PLoS Negl Trop Dis. 2015 Jul 28;9(7):e0003959
pubmed: 26217948
Int J Parasitol. 2006 Oct;36(12):1241-4
pubmed: 16930605
Rev Inst Med Trop Sao Paulo. 1972 Nov-Dec;14(6):397-400
pubmed: 4675644
J Parasitol. 1996 Aug;82(4):557-64
pubmed: 8691363
Infect Dis Poverty. 2017 Mar 22;6(1):63
pubmed: 28327187
Parasitology. 2014 Dec;141(14):1841-55
pubmed: 24932595
PLoS Negl Trop Dis. 2014 Nov 20;8(11):e3286
pubmed: 25412105
Curr Opin Infect Dis. 2008 Dec;21(6):659-67
pubmed: 18978535
PLoS Negl Trop Dis. 2017 Feb 17;11(2):e0005372
pubmed: 28212414
Int J Epidemiol. 2015 Feb;44(1):87-97
pubmed: 25433704
Lancet. 2014 Jun 28;383(9936):2253-64
pubmed: 24698483
Parasit Vectors. 2018 Feb 23;11(1):111
pubmed: 29475457
Front Immunol. 2019 Apr 04;10:682
pubmed: 31019510
Expert Rev Anti Infect Ther. 2013 Nov;11(11):1237-58
pubmed: 24127662
Parasit Vectors. 2018 Oct 23;11(1):552
pubmed: 30352631
Exp Parasitol. 1986 Jun;61(3):294-303
pubmed: 3086114
Infect Dis Poverty. 2017 Jun 16;6(1):110
pubmed: 28622767
mBio. 2016 Aug 09;7(4):
pubmed: 27507822
Trans R Soc Trop Med Hyg. 2004 Jan;98(1):18-27
pubmed: 14702835
BMC Infect Dis. 2018 Dec 14;18(1):662
pubmed: 30547750
Am J Trop Med Hyg. 2016 Feb;94(2):361-4
pubmed: 26556831
Parasitology. 2001 May;122(Pt 5):537-44
pubmed: 11393827
Am J Trop Med Hyg. 2013 Jul;89(1):46-50
pubmed: 23716406
PLoS Negl Trop Dis. 2013;7(3):e2109
pubmed: 23556011
PLoS Negl Trop Dis. 2018 Dec 14;12(12):e0006941
pubmed: 30550594
Parasite Immunol. 2014 Aug;36(8):347-57
pubmed: 25142505
Nat Rev Dis Primers. 2018 Aug 9;4(1):13
pubmed: 30093684
Front Public Health. 2015 Mar 19;3:48
pubmed: 25853117
PLoS Negl Trop Dis. 2014 Sep 11;8(9):e3139
pubmed: 25211217
Am J Trop Med Hyg. 2013 Mar;88(3):426-432
pubmed: 23339198
Am J Trop Med Hyg. 2016 Mar;94(3):605-610
pubmed: 26755565
J Biomed Inform. 2019 Jul;95:103208
pubmed: 31078660
J Infect Dis. 2014 Dec 15;210(12):2009-16
pubmed: 25001462
Am J Trop Med Hyg. 1996 Apr;54(4):319-24
pubmed: 8615440
PLoS Negl Trop Dis. 2015 Feb 19;9(2):e0003504
pubmed: 25695740
Acta Trop. 2019 Nov;199:105150
pubmed: 31425672
Biomed Res Int. 2017;2017:7035025
pubmed: 29094048
Am J Trop Med Hyg. 2019 Mar;100(3):578-583
pubmed: 30608053
J Infect Dis. 1999 Apr;179(4):996-1003
pubmed: 10068597
Int J Parasitol. 2005 Nov;35(13):1453-7
pubmed: 16002073