Clinical trial NCT02143934: Effect of Liver and Blood-stage Treatment on Subsequent Plasmodium Reinfection and Morbidity
Official title: Host and Parasites Factors Contributing to Risk of Plasmodium Re-infection and Morbidity in Elementary School Children in Maprik, East Sepik Province
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Plasmodium Vivax Infection
Plasmodium Vivax Clinical Episode
Plasmodium Falciparum Infection
Plasmodium Falciparum Clinical Episode
Keywords: Plasmodium vivax
Hypnozoites
Primaquine
Liver-stage
Blood-stage
Plasmodium falciparum
Lead sponsor: Papua New Guinea Institute of Medical Research
Sponsor class: OTHER_GOV
Collaborators: name: Walter and Eliza Hall Institute of Medical Research
name: Swiss Tropical & Public Health Institute
name: Barcelona Centre for International Health Research
First posted: 2014-05-21
Enrollment: 524
Sex: ALL
Minimum age (years): 5
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This study specifically seeks to quantify the contribution of relapes to the burden of P. vivax infections and disease by determining on the effect of radical pre-erythrocytic and erythrocytic clearance on subsequent rates of Plasmodium spp. infection and disease in children aged 5-10 years in a treatment to re-infection study design. In order the clear liver-stage/blood-stages G6PD-normal children were randomised to receive Chloroquine (3 days, standard dose) and Coartem (3 days, standard dose) plus either i) primaquine (20 days, 0.5mg/kg) or ii) placebo (20days). These drugs were administered over a period of 4 weeks.

In addition to this epidemiological data, the study will assess the natural acquisition of cellular and humoral immune responses to P. falciparum and P. vivax, thus assisting in the determination of correlates of clinical immunity to P. falciparum and P. vivax in PNG children aged 5-10 years.

These data will not only be essential for development of future vaccines against P. vivax and P falciparum but provide invaluable insight into the contribution of long-lasting liver-stages to the force of infection with P. vivax that will contribute towards designing more rational approaches to the treatment of P. vivax both in the context of case management and future attempts at elimination.


Eligibility criteria: Inclusion Criteria:

* aged 5-10 years (±3 months)
* permanent residents of the area
* absence of history of hypersensitivity reactions to the drugs

Exclusion Criteria:

* chronic illness
* severe malnutrition (weight-for-age nutritional Z score \[WAZ\] \<60th percentile)
* severe anemia (Hb \<5 g/dL),
* G-6-PD deficiency (\<60% G-6-PD activity)
* permanent disability, which prevents or impedes study participation. Any 1 or more of the criteria is sufficient to exclude study participation.

Primary outcomes:
measure: Time to first or only Plasmodium vivax infection by light microscopy and PCR
timeFrame: 8 months post-baseline
measure: Time to first or only clinical P. vivax episode
timeFrame: 8 months post-baseline
Secondary outcomes:
measure: Time to first or only P. falciparum infection by light microscopy and PCR
timeFrame: 8 months post-baseline
measure: Time to first or only P. ovale infection by light microscopy and PCR
timeFrame: 8 months post-baseline
measure: Time to first or only P. malariae infection by light microscopy and PCR
timeFrame: 8 months post-baseline
Other outcomes:
Locations:
city: Maprik
country: Papua New Guinea
facility: PNG Institute of Medical Research
state: East Sepik Province
Study officials:
affiliation: Walter and Eliza Hall Institute of Medical Research; Centre de Recerca en Salut Internacional de Barcelona (CRESIB)
name: Ivo Mueller, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: PNG Institute of Medical Research
name: Inoni Betuela, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Walter and Eliza Hall Institute of Medical Research
name: Louis Schofield, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Holzschuh A, Gruenberg M, Hofmann NE, Wampfler R, Kiniboro B, Robinson LJ, Mueller I, Felger I, White MT. Co-infection of the four major Plasmodium species: Effects on densities and gametocyte carriage. PLoS Negl Trop Dis. 2022 Sep 13;16(9):e0010760. doi: 10.1371/journal.pntd.0010760. eCollection 2022 Sep.
citation: Hofmann NE, Karl S, Wampfler R, Kiniboro B, Teliki A, Iga J, Waltmann A, Betuela I, Felger I, Robinson LJ, Mueller I. The complex relationship of exposure to new Plasmodium infections and incidence of clinical malaria in Papua New Guinea. Elife. 2017 Sep 1;6:e23708. doi: 10.7554/eLife.23708.
citation: Wampfler R, Hofmann NE, Karl S, Betuela I, Kinboro B, Lorry L, Silkey M, Robinson LJ, Mueller I, Felger I. Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum. PLoS Negl Trop Dis. 2017 Jul 21;11(7):e0005753. doi: 10.1371/journal.pntd.0005753. eCollection 2017 Jul.
citation: Robinson LJ, Wampfler R, Betuela I, Karl S, White MT, Li Wai Suen CS, Hofmann NE, Kinboro B, Waltmann A, Brewster J, Lorry L, Tarongka N, Samol L, Silkey M, Bassat Q, Siba PM, Schofield L, Felger I, Mueller I. Strategies for understanding and reducing the Plasmodium vivax and Plasmodium ovale hypnozoite reservoir in Papua New Guinean children: a randomised placebo-controlled trial and mathematical model. PLoS Med. 2015 Oct 27;12(10):e1001891. doi: 10.1371/journal.pmed.1001891. eCollection 2015 Oct.