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

Condition(s) targeted: Plasmodium Vivax Infection; Plasmodium Vivax Clinical Episode; Plasmodium Falciparum Infection; Plasmodium Falciparum Clinical Episode

Intervention: Primaquine (Drug); Placebo (Drug); Chloroquine (Drug); Artemether Lumefantrine (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Papua New Guinea Institute of Medical Research

Official(s) and/or principal investigator(s):
Ivo Mueller, PhD, Principal Investigator, Affiliation: Walter and Eliza Hall Institute of Medical Research; Centre de Recerca en Salut Internacional de Barcelona (CRESIB)
Inoni Betuela, MD PhD, Principal Investigator, Affiliation: PNG Institute of Medical Research
Louis Schofield, PhD, Principal Investigator, Affiliation: Walter and Eliza Hall Institute of Medical Research

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science

Primary outcome:

Time to first or only Plasmodium vivax infection by light microscopy and PCR

Time to first or only clinical P. vivax episode

Secondary outcome:

Time to first or only P. falciparum infection by light microscopy and PCR

Time to first or only P. ovale infection by light microscopy and PCR

Time to first or only P. malariae infection by light microscopy and PCR

Minimum age: 5 Years. Maximum age: 10 Years. Gender(s): Both.

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.

PNG Institute of Medical Research, Maprik, East Sepik Province, Papua New Guinea

Starting date: August 2009
Last updated: May 19, 2014