Artemisinin-Based Combination Treatment of falciparum Malaria

Shoklo Malaria Research Unit, Mae Sot, Thailand.
The American journal of tropical medicine and hygiene (Impact Factor: 2.7). 11/2008; 77(6 Suppl):181-92.
Source: PubMed


Artemisinin-based combination treatments (ACTs) are now generally accepted as the best treatments for uncomplicated falciparum malaria. They are rapidly and reliably effective. Efficacy is determined by the drug partnering the artemisinin derivative and, for artesunate-mefloquine, artemether-lumefantrine, and dihydroartemisinin-piperaquine, this usually exceeds 95%. Artesunate-sulfadoxine-pyrimethamine and artesunate-amodiaquine are effective in some areas, but in other areas resistance to the partner precludes their use. There is still uncertainty over the safety of artemisinin derivatives in the first trimester of pregnancy, when they should not be used unless there are no effective alternatives. Otherwise, except for occasional hypersensitivity reactions, the artemisinin derivatives are safe and remarkably well tolerated. The adverse effect profiles of the artemisinin-based combination treatments are determined by the partner drug. Most malaria endemic countries have now adopted artemisinin-based combination treatments as first-line treatment of falciparum malaria, but in most of these only a minority of the patients that need artemisinin-based combination treatments actually receive them.

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    • "These partner drugs (e.g., PQ, mefloquine, amodiaquine, lumefantrine, pyronaridine ) are eliminated slowly compared to the artemisinin derivatives (e.g., DHA, artesunate, artemether), which are eliminated rapidly, although they swiftly bring down the parasite biomass[3]. This provides protection for the artemisinin derivative while the partner drugs provide prolonged drug cover[4]. The half-life of PQ is 21–28 days567, longer than most of the partner drugs used in ACT, providing a longer post-treatment prophylactic effect compared to lumefantrine (3–5 days)[3,8], the active amodiaquine metabolite desethylamodiaquine (7–12 days)[9], mefloquine (17–24 days)[10], and pyronaridine (13.2 and 9.6 days in adults and children, respectively)[11]. "
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    ABSTRACT: Dihydroartemisinin-piperaquine (DHA-PQ) is one of five WHO recommended artemisinin combination therapy (ACT) for the treatment of uncomplicated malaria. However, little was known on its post-registration safety and effectiveness in sub-Saharan Africa. DHA-PQ provides a long post-treatment prophylactic effect against re-infection; however, new infections have been reported within a few weeks of treatment, especially in children. This paper reports the clinical outcomes following administration of DHQ-PQ in real-life conditions in public health facilities in Burkina Faso, Ghana, Mozambique, and Tanzania for the treatment of confirmed uncomplicated malaria. An observational, non-comparative, longitudinal study was conducted on 10,591 patients with confirmed uncomplicated malaria visiting public health facilities within seven health and demographic surveillance system sites in four African countries (Ghana, Tanzania, Burkina Faso, Mozambique) between September 2013 and April 2014. Patients were treated with DHA-PQ based on body weight and followed up for 28 days to assess the clinical outcome. A nested cohort of 1002 was intensely followed up. Clinical outcome was assessed using the proportion of patients who reported signs and symptoms of malaria after completing 3 days of treatment. A total of 11,097 patients were screened with 11,017 enrolled, 94 were lost to follow-up, 332 withdrew and 10,591 (96.1 %) patients aged 6 months–85 years met protocol requirements for analysis. Females were 52.8 and 48.5 % were <5 years of age. Malaria was diagnosed by microscopy and rapid diagnostic test in 69.8 % and 29.9 %, respectively. At day 28, the unadjusted risk of recurrent symptomatic parasitaemia was 0.5 % (51/10,591). Most of the recurrent symptomatic malaria patients (76 %) were children <5 years. The mean haemoglobin level decreased from 10.6 g/dl on day 1 to 10.2 g/dl on day 7. There was no significant renal impairment in the nested cohort during the first 7 days of follow-up with minimal non-clinically significant changes noted in the liver enzymes. DHA-PQ was effective and well tolerated in the treatment of uncomplicated malaria and provides an excellent alternative first-line ACT in sub-Saharan Africa.
    Full-text · Article · Dec 2016 · Malaria Journal
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    • "Author(s) agree that this article remains permanently open access under the terms of the Creative Commons Attribution License 4.0 International License (Nosten and White, 2007). Since the adoption of the ACT policy in many regions where P. falciparum malaria is endemic (Bosman and Mendis, 2007), a trend of steady reduction in global malaria incidence has been observed (WHO, 2011). "

    Preview · Article · Jan 2015 · AFRICAN JOURNAL OF BIOTECHNOLOGY
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    • "The relatively high cost of these antimalarials has made their manufacture a lucrative venture for pharmaceutical industries; a situation that has led to the proliferation of diverse brands on the market. This has led some unscrupulous people to indulge in the manufacture of substandard and falsified brands [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]. The WHO acknowledges the difficulty that this situation presents to the quality assurance of antimalarials on the market, especially in developing countries where enforcement of laws regarding manufacture, importation , and distribution of medicines is relatively lax. "
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    ABSTRACT: This study, conducted as part of our overall goal of regular pharmacovigilance of antimalarial medicines, reports on the quality of 132 artemisinin-based antimalarial medicines distributed in Ghana and Togo. Three methods were employed in the quality evaluation-basic (colorimetric) tests for establishing the identity of the requisite active pharmaceutical ingredients (APIs), semi-quantitative TLC assay for the identification and estimation of API content, and HPLC assay for a more accurate quantification of API content. From the basic tests, only one sample totally lacked API. The HPLC assay, however, showed that 83.7% of the ACTs and 57.9% of the artemisinin-based monotherapies failed to comply with international pharmacopoeia requirements due to insufficient API content. In most of the ACTs, the artemisinin component was usually the insufficient API. Generally, there was a good correlation between the HPLC and SQ-TLC assays. The overall failure rates for both locally manufactured (77.3%) and imported medicines (77.5%) were comparable. Similarly the unregistered medicines recorded a slightly higher overall failure rate (84.7%) than registered medicines (70.8%). Only two instances of possible cross-border exchange of medicines were observed and there was little difference between the medicine quality of collections from border towns and those from inland parts of both countries.
    Full-text · Article · Oct 2014 · Malaria Research and Treatment
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