Efficacy and safety of dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum malaria in endemic countries: meta-analysis of randomized controlled trials

School of Postgraduate Studies and Research, International Medical University (IMU), Kuala Lumpur 57000, Malaysia.
Transactions of the Royal Society of Tropical Medicine and Hygiene (Impact Factor: 1.84). 12/2012; 107(2). DOI: 10.1093/trstmh/trs019
Source: PubMed


The present review aimed to synthesise available evidence on the efficacy of dihydroartemisinin-piperaquine (DP) in treating uncomplicated Plasmodium falciparum malaria in people living in malaria-endemic countries by performing a meta-analysis of relevant studies. We searched relevant studies in electronic data bases up to December 2011. Published results from randomised controlled trials (RCTs) comparing efficacy of DP with other artemisinin-based combination therapies (ACTs), or non-ACTs, or placebo were selected. The primary endpoint was 28-day and 42-day treatment failure. We identified 26 RCTs. Many of the studies included in the present review were of high quality. Overall, DP, artesunate-mefloquine (MAS3) and artemether-lumefentrine (AL) were equally effective for reducing the risk of recurrent parasitaemia. The PCR confirmed efficacy of DP (99.5%) and MAS3 (97.7%) at day 28 exceeded 90%; both are efficacious. Comparable efficacy was also found for DP (95.6%) and AL (94.3%). The present review has documented that DP is comparable to other currently used ACTs such as MAS3 and AL in treating uncomplicated falciparum malaria. The better safety profile of DP and once-daily dosage improves adherence and its fixed co-formulation ensures that both drugs are taken together. Our conclusion is that DP has the potential to become a first-line antimalarial drug.

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    • "No review had comprehensively compared these two ACTs head-to-head to determine their relative prophylactic effectiveness. Earlier reviews [17, 18] had not explored prophylaxis specifically in detail. "
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    ABSTRACT: Malaria contributes significantly to the global disease burden. The World Health Organization recommended the use of artemisinin-based combination therapies (ACTs) for treatment of uncomplicated falciparum malaria a decade ago in response to problems of drug resistance. This review compared two of the ACTs-Dihydroartemisinin-Piperaquine (DP) and Artemether-Lumefantrine (AL) to provide evidence which one has the ability to offer superior posttreatment prophylaxis at 28 and 42 days posttreatment. Four databases (MEDLINE, EMBASE, Cochrane Database and Global Health) were searched on June 2, 2013 and a total of seven randomized controlled trials conducted in sub-Sahara Africa were included. Results involving 2, 340 participants indicates that reduction in risk for recurrent new falciparum infections (RNIs) was 79% at day 28 in favour of DP [RR, 0.21; 95% CI: 0.14 to 0.32, P < 0.001], and at day 42 was 44% favouring DP [RR, 0.56; 95% CI: 0.34 to 0.90; P = 0.02]. No significant difference was seen in treatment failure rates between the two drugs at days 28 and 42. It is concluded that use of DP offers superior posttreatment prophylaxis compared to AL in the study areas. Hence DP can help reduce malaria cases in such areas more than AL.
    Malaria Research and Treatment 06/2014; 2014. DOI:10.1155/2014/263674
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    • "The objective was to develop and gain international regulatory approval for use of the fixed-dose ACT DHA-PQP (brand name Eurartesim®). The combination of DHA-PQP (under other brand names from other manufacturers) had been used widely and demonstrated usefulness as a key treatment against malaria in the private sector in certain countries in Asia and Africa [3-8]. With the emergence of resistance to artemisinin and its derivatives in south-east Asia, WHO’s Global plan for artemisinin resistance containment (GPARC) calls for improved access to quality-assured diagnostics and treatment with ACT [9]. "
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    ABSTRACT: Background This case study describes how a public-private partnership between Medicines for Malaria Venture (MMV) and Sigma-Tau Industrie Farmaceutiche Riunite SpA achieved international regulatory approval for use of the fixed-dose artemisinin-based combination therapy dihydroartemisinin-piperaquine (Eurartesim®) for the treatment of malaria, enabling more widespread access to the medicine in malaria-endemic countries. Case description The combination of dihydroartemisinin and piperaquine demonstrated success in clinical trials for the treatment of malaria in Asia and Africa in the 2000s. However, as it had not been developed to international regulatory standards it was out of the reach of the majority of patients in disease-endemic countries, particularly those reliant on public healthcare systems supported by international donor funding. To overcome this, as of 2004 MMV worked in partnership with Sigma-Tau, Holleykin, Oxford University, the Institute of Tropical Medicine Antwerp, and the National Institute of Malaria Research India to develop the dihydroartemisinin-piperaquine combination to international standards. In 2011, the European Commission granted full marketing authorization to Sigma-Tau for Eurartesim. Discussion and evaluation The partnership between MMV, Sigma-Tau, and numerous other academic and industrial partners across the world, led to the successful development to EMA regulatory standards of a high-quality and highly efficacious anti-malarial treatment that otherwise would not have been possible. The dossier has also been submitted to the WHO for prequalification, and a safety statement to guide correct use of Eurartesim has been produced. In July 2012, the first delivery to a disease-endemic country was made to Cambodia, where the medicine is being used to treat patients and help counter the emergence of artemisinin resistance in the area. A paediatric dispersible formulation of Eurartesim is being developed, with the objective to submit the dossier to the EMA by the end of 2014. Conclusions The development of Eurartesim to international regulatory standards exemplifies the strengths of the product development partnership model in utilising the individual skills and expertise of partners with differing objectives to achieve a common goal. Successful uptake of Eurartesim by public health systems in malaria-endemic countries poses new challenges, which may require additional partnerships as we move forward.
    Malaria Journal 06/2013; 12(1):211. DOI:10.1186/1475-2875-12-211 · 3.11 Impact Factor
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    ABSTRACT: A steadily increasing number of Western travellers are exposed to malaria. Also, numbers of migrants from malarious areas are increasing. Fast and effective treatment options are needed to ensure effective malaria treatment in these groups in the future. Artemisinin combinations are well tolerated and have shown high efficacy in malaria endemic areas. Since 2001, 42 malaria endemic countries, 23 of them in Africa, have adopted artemisinin based combination therapies recommended by WHO. An additional 14 countries are in the process of changing their malaria treatment policy. Studies in non-immune travellers confirm a rapid parasite clearance time and very low rate of side effects. Outpatient clinics and hospitals in non-endemic countries should have standard operating procedures for diagnosing and managing patients with malaria. In this setting, artemisinin combinations should be available for treatment of uncomplicated malaria as they are clearly superior to any other oral antimalarial in their fast reduction of parasite biomass and in decreasing clinical symptoms. Also, they are the drugs of choice for travellers who are advised to carry stand-by emergency treatment during their journey.
    Travel Medicine and Infectious Disease 02/2013; 11(1). DOI:10.1016/j.tmaid.2013.01.005 · 1.67 Impact Factor
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