Parasite Clearance and Protection From Infection (PCPI) in Cameroon

Summary

The Cameroon PCPI study will measure the effect of the parasite genotypes associated with SP resistance on parasite clearance and protection from infection when exposed to SP. The total number of participants is expected to be 900 healthy between 3 to 5 years old who have no symptoms of malaria infection of which 450 children will be assigned to the SP group, 250 to the SPAQ group, and 200 to the AS group. The results of this study will allow to measure the effect of the parasite genotypes associated with SP resistance on parasite clearance and protection from infection when exposed to SP.

Timeline

Start

2024-06-10

Primary completion

2024-12-25

Completion

2025-03-05

Publications

• Background Schellenberg D, Menendez C, Kahigwa E, Aponte J, Vidal J, Tanner M, Mshinda H, Alonso P. Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial. Lancet. 2001 May 12;357(9267):1471-7. doi: 10.1016/S0140-6736(00)04643-2.
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• Background Kobbe R, Kreuzberg C, Adjei S, Thompson B, Langefeld I, Thompson PA, Abruquah HH, Kreuels B, Ayim M, Busch W, Marks F, Amoah K, Opoku E, Meyer CG, Adjei O, May J. A randomized controlled trial of extended intermittent preventive antimalarial treatment in infants. Clin Infect Dis. 2007 Jul 1;45(1):16-25. doi: 10.1086/518575. Epub 2007 May 29.
• Background Mockenhaupt FP, Reither K, Zanger P, Roepcke F, Danquah I, Saad E, Ziniel P, Dzisi SY, Frempong M, Agana-Nsiire P, Amoo-Sakyi F, Otchwemah R, Cramer JP, Anemana SD, Dietz E, Bienzle U. Intermittent preventive treatment in infants as a means of malaria control: a randomized, double-blind, placebo-controlled trial in northern Ghana. Antimicrob Agents Chemother. 2007 Sep;51(9):3273-81. doi: 10.1128/AAC.00513-07. Epub 2007 Jul 16.
• Background Grobusch MP, Lell B, Schwarz NG, Gabor J, Dornemann J, Potschke M, Oyakhirome S, Kiessling GC, Necek M, Langin MU, Klein Klouwenberg P, Klopfer A, Naumann B, Altun H, Agnandji ST, Goesch J, Decker M, Salazar CL, Supan C, Kombila DU, Borchert L, Koster KB, Pongratz P, Adegnika AA, Glasenapp Iv, Issifou S, Kremsner PG. Intermittent preventive treatment against malaria in infants in Gabon--a randomized, double-blind, placebo-controlled trial. J Infect Dis. 2007 Dec 1;196(11):1595-602. doi: 10.1086/522160. Epub 2007 Oct 25.
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• Background Oguike MC, Falade CO, Shu E, Enato IG, Watila I, Baba ES, Bruce J, Webster J, Hamade P, Meek S, Chandramohan D, Sutherland CJ, Warhurst D, Roper C. Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V. Int J Parasitol Drugs Drug Resist. 2016 Dec;6(3):220-229. doi: 10.1016/j.ijpddr.2016.08.004. Epub 2016 Sep 29.
• Background ACCESS-SMC Partnership. Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study. Lancet. 2020 Dec 5;396(10265):1829-1840. doi: 10.1016/S0140-6736(20)32227-3.
• Background World Health Organisation. Malaria chemoprevention efficacy study protocol. Geneva: World Health Organisation, 2022.
• Background World Health Organization. WHO policy recommendation on intermittent preventive treatment during infancy with sulphadoxine-pyrimethamine (SP-IPTi) for plasmodium falciparum malaria control in Africa: World Health Organization, 2010.
• Background Esu EB, Oringanje C, Meremikwu MM. Intermittent preventive treatment for malaria in infants. Cochrane Database Syst Rev. 2021 Jul 17;7(7):CD011525. doi: 10.1002/14651858.CD011525.pub3.
• Background Sutherland CJ, Fifer H, Pearce RJ, bin Reza F, Nicholas M, Haustein T, Njimgye-Tekumafor NE, Doherty JF, Gothard P, Polley SD, Chiodini PL. Novel pfdhps haplotypes among imported cases of Plasmodium falciparum malaria in the United Kingdom. Antimicrob Agents Chemother. 2009 Aug;53(8):3405-10. doi: 10.1128/AAC.00024-09. Epub 2009 May 11.
• Background Beshir KB, Muwanguzi J, Nader J, Mansukhani R, Traore A, Gamougam K, Ceesay S, Bazie T, Kolie F, Lamine MM, Cairns M, Snell P, Scott S, Diallo A, Merle CS, NDiaye JL, Razafindralambo L, Moroso D, Ouedraogo JB, Zongo I, Kessely H, Doumagoum D, Bojang K, Ceesay S, Loua K, Maiga H, Dicko A, Sagara I, Laminou IM, Ogboi SJ, Eloike T, Milligan P, Sutherland CJ. Prevalence of Plasmodium falciparum haplotypes associated with resistance to sulfadoxine-pyrimethamine and amodiaquine before and after upscaling of seasonal malaria chemoprevention in seven African countries: a genomic surveillance study. Lancet Infect Dis. 2023 Mar;23(3):361-370. doi: 10.1016/S1473-3099(22)00593-X. Epub 2022 Oct 31.
• Background Chijioke-Nwauche I, Oguike MC, Nwauche CA, Beshir KB, Sutherland CJ. Antimalarial drug resistance markers in human immunodeficiency virus (HIV)-positive and HIV-negative adults with asymptomatic malaria infections in Port Harcourt, Nigeria. Trans R Soc Trop Med Hyg. 2021 May 8;115(5):531-537. doi: 10.1093/trstmh/trab061.
• Background Wang P, Sims PF, Hyde JE. A modified in vitro sulfadoxine susceptibility assay for Plasmodium falciparum suitable for investigating Fansidar resistance. Parasitology. 1997 Sep;115 ( Pt 3):223-30. doi: 10.1017/s0031182097001431.
• Background Kimura I, Miyamoto J, Ohue-Kitano R, Watanabe K, Yamada T, Onuki M, Aoki R, Isobe Y, Kashihara D, Inoue D, Inaba A, Takamura Y, Taira S, Kumaki S, Watanabe M, Ito M, Nakagawa F, Irie J, Kakuta H, Shinohara M, Iwatsuki K, Tsujimoto G, Ohno H, Arita M, Itoh H, Hase K. Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice. Science. 2020 Feb 28;367(6481):eaaw8429. doi: 10.1126/science.aaw8429.
• Background Waltmann A, McQuade ETR, Chinkhumba J, Operario DJ, Mzembe E, Itoh M, Kayange M, Puerto-Meredith SM, Mathanga DP, Juliano JJ, Carroll I, Bartelt LA, Gutman JR, Meshnick SR. The positive effect of malaria IPTp-SP on birthweight is mediated by gestational weight gain but modifiable by maternal carriage of enteric pathogens. EBioMedicine. 2022 Mar;77:103871. doi: 10.1016/j.ebiom.2022.103871. Epub 2022 Feb 23.
• Background Gimnig JE, MacArthur JR, M'bang'ombe M, Kramer MH, Chizani N, Stern RS, Mkandala C, Newman RD, Steketee RW, Campbell CH. Severe cutaneous reactions to sulfadoxine-pyrimethamine and trimethoprim-sulfamethoxazole in Blantyre District, Malawi. Am J Trop Med Hyg. 2006 May;74(5):738-43.
• Background Taylor WR, White NJ. Antimalarial drug toxicity: a review. Drug Saf. 2004;27(1):25-61. doi: 10.2165/00002018-200427010-00003.
• Background Adeleke OT, Oyenuga A, Slusher TM, Gbadero DA. Cluster-randomized controlled trial of intermittent preventive treatment in infancy using sulfadoxine-pyrimethamine (SP-IPTi): a pilot study in Nigeria. J Trop Pediatr. 2022 Dec 5;69(1):fmad001. doi: 10.1093/tropej/fmad001.
• Background Wilson AL; IPTc Taskforce. A systematic review and meta-analysis of the efficacy and safety of intermittent preventive treatment of malaria in children (IPTc). PLoS One. 2011 Feb 14;6(2):e16976. doi: 10.1371/journal.pone.0016976.
• Background Cairns M, Cisse B, Sokhna C, Cames C, Simondon K, Ba EH, Trape JF, Gaye O, Greenwood BM, Milligan PJ. Amodiaquine dosage and tolerability for intermittent preventive treatment to prevent malaria in children. Antimicrob Agents Chemother. 2010 Mar;54(3):1265-74. doi: 10.1128/AAC.01161-09. Epub 2010 Jan 11.
• Background Bakai TA, Thomas A, Iwaz J, Atcha-Oubou T, Tchadjobo T, Khanafer N, Rabilloud M, Voirin N. Effectiveness of seasonal malaria chemoprevention in three regions of Togo: a population-based longitudinal study from 2013 to 2020. Malar J. 2022 Dec 31;21(1):400. doi: 10.1186/s12936-022-04434-w.
• Background Sokhna C, Cisse B, Ba el H, Milligan P, Hallett R, Sutherland C, Gaye O, Boulanger D, Simondon K, Simondon F, Targett G, Lines J, Greenwood B, Trape JF. A trial of the efficacy, safety and impact on drug resistance of four drug regimens for seasonal intermittent preventive treatment for malaria in Senegalese children. PLoS One. 2008 Jan 23;3(1):e1471. doi: 10.1371/journal.pone.0001471.
• Results World Health Organization. WHO guidelines for malaria, 3 June 2022: World Health Organization, 2022.
• Results Aponte JJ, Schellenberg D, Egan A, Breckenridge A, Carneiro I, Critchley J, Danquah I, Dodoo A, Kobbe R, Lell B, May J, Premji Z, Sanz S, Sevene E, Soulaymani-Becheikh R, Winstanley P, Adjei S, Anemana S, Chandramohan D, Issifou S, Mockenhaupt F, Owusu-Agyei S, Greenwood B, Grobusch MP, Kremsner PG, Macete E, Mshinda H, Newman RD, Slutsker L, Tanner M, Alonso P, Menendez C. Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials. Lancet. 2009 Oct 31;374(9700):1533-42. doi: 10.1016/S0140-6736(09)61258-7. Epub 2009 Sep 16.
• Martinez-Vega R, Mbacham WF, Ali I, Nji A, Mousa A, Beshir KB, Chopo-Pizarro A, Kaur H, Okell L, Hansson H, Hocke EF, Alifrangis M, Gosling R, Roper C, Sutherland C, Chico RM. Parasite clearance and protection from Plasmodium falciparum infection (PCPI): a three-arm, parallel, double-blinded, placebo-controlled, randomised trial of presumptive sulfadoxine-pyrimethamine versus sulfadoxine-pyrimethamine plus amodiaquine versus artesunate monotherapy among asymptomatic children 3-5 years of age in Cameroon. BMC Infect Dis. 2024 Sep 26;24(1):1028. doi: 10.1186/s12879-024-09868-y.

Drugs

Indications