The treatment of malaria in Papua New Guinean children

Moses Laman

    Research output: ThesisDoctoral Thesis

    505 Downloads (Pure)

    Abstract

    [Truncated] In Papua New Guinea (PNG), malaria is endemic for Plasmodium falciparum,P. vivax, P. malariae and P. ovale infections. The predominant species are P.falciparum and P. vivax. Despite the declining incidence of P. falciparum globally, P.vivax remains a major obstacle to malaria control programs because of its complex lifecycle and transmission biology. This was evident in a previously-published four-armclinical trial in which artemether-lumefantrine (AL) was the most efficacious artemisinin-based combination therapy (ACT) in PNG children with falciparum malaria while dihydroarthemisinin-piperaquine (DP) was the most efficacious for vivax malaria. However, the impracticality of species-specific treatments in most malaria-endemicsettings highlights the need for ACTs that are safe and efficacious against multiple Plasmodium species. Of few available alternatives, artemisinin-naphthoquine (ARTNQ) is already widely available in many countries in Africa, Asia and Oceania as a single-dose therapy. However, ART-NQ has not met the World Health Organisation (WHO) pre-registration requirements and the manufacturer's single dose recommendation is not in line with WHO stipulations that all ACTs should be given for not less than 3 days.

    The efficacy, tolerability, safety and post-treatment prophylactic effectiveness of AL, recommended first-line treatment in PNG, was compared to three daily doses of ART-NQ in an open-label, randomised, parallel-group trial. Patients were followed upon Days 1, 2, 3, 7, 14, 28 and 42. Primary endpoints were the Day 42 P. falciparum polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) and the P. vivax PCR-uncorrected Day 42 ACPR. For falciparum malaria, a 5% non-inferiority design was used, while a superiority design was used for vivax malaria. Because the present study is the first to employ ART-NQ as a three-dose regimen in young children rather than the single dose specified by the manufacturer, detailed safety monitoring was performed. The safety phase comprised of serial haematological and hepatorenal monitoring as well as electrocardiographic QTc interval assessments during the first week after treatment. The accuracy of the World Health Organization method of estimating malaria parasite density from thick blood smears by assuming a white blood cell count of 8,000/μL was also validated in the present study. At six months after initial treatment, documentation available for a subset of participants was assessed for episodes of clinical malaria. Children who participated in a study of post-treatment changes in splenic volume were assessed as part of follow-up in the main trial.

    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - Jan 2015

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