Effect of Liver and Blood-stage Treatment on Subsequent Plasmodium Reinfection and Morbidity

Study Overview
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Brief Summary
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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.

Official Title
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Host and Parasites Factors Contributing to Risk of Plasmodium Re-infection and Morbidity in Elementary School Children in Maprik, East Sepik Province

Conditions
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Plasmodium Vivax Infection, Plasmodium Vivax Clinical Episode, Plasmodium Falciparum Infection, Plasmodium Falciparum Clinical Episode

Intervention / Treatment
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* Drug: Primaquine
* Drug: Placebo
* Drug: Chloroquine
* Drug: Artemether Lumefantrine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Primaquine<br>Primaquine, 0.5mg/kg/day, 20 days directly observed treatment Chloroquine, 25mg/kg total dose, divided over 3 days directly observed treatment Artemether-Lumefantrine, 3 days BD | Drug: Primaquine<br> <br> Drug: Chloroquine<br> <br> Drug: Artemether Lumefantrine<br> <br> * Other names: Coartem;|
| Placebo Comparator: Placebo<br>Placebo, 20 days directly observed treatment Chloroquine, mg/kg, 3 days directly observed treatment Artemether-Lumefantrine, 3 days BD | Drug: Placebo<br>* Sugar pills, appearance identical to Primaquine tablets<br>Drug: Chloroquine<br> <br> Drug: Artemether Lumefantrine<br> <br> * Other names: Coartem;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first or only Plasmodium vivax infection by light microscopy and PCR |  | 8 months post-baseline | 
| Time to first or only clinical P. vivax episode |  | 8 months post-baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first or only P. falciparum infection by light microscopy and PCR |  | 8 months post-baseline | 
| Time to first or only P. ovale infection by light microscopy and PCR |  | 8 months post-baseline | 
| Time to first or only P. malariae infection by light microscopy and PCR |  | 8 months post-baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plasmodium vivax, Hypnozoites, Primaquine, Liver-stage, Blood-stage, Plasmodium falciparum