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Background: Malaria still a public health problem in the tropics and subtropics areas, particularly in South East Asia (SEA) and Subsaharan, Africa. Achievements of National Malaria Control Program in Vietnam cannot be made without significant contribution of highly effective antimalarial drugs. The introduction of artemisinine helped to contain resistance in the context of P. falciparum showing low response and high resistance to quinine, chloroquine, and mefloquine. During 2000 – 2011, some in vitro and in vivo results found artemisinine and its derivatives had declined efficacy against P. falciparum (WHO., 2011), in line with some health facilities in Central and Westhighland provinces reported that reduced efficacy of ACTs on several clinical cases (H.H.Quang et al., 2011). The emergence and spread of drug-resistant malaria parasites, especially in dangerous Plasmodium falciparum species, is the major threat to effective malaria control. The artemisinin derivatives have had an important clinical impact both on the treatment of multi drug resistant falciparum malaria. However, experience has shown that resistance eventually curtails the life span of drugs. If measures are not applied to contain resistance, the investment put into the development of new drugs will be squandered. Therefore, in parallel with the monitoring of the efficacy of currently-used drugs, the evaluation of novel ACTs for replacing and overcoming the backwards of the old ones is really essential to suggest possible changes in the national drug policy. Objectives: The study is designed to evaluate the efficacy of artesunate monotherapy 7 days regimen and some artemisinine based combination therapies (ACTs) on uncomplicated P. falciparum malaria patients, and assess some possible side effects from these regimens Methods: with study design of clinical trials of in vivo in the community based-fields, and treatment outcomes classification by the latest update WHO guidance in 2009, including ACPR (Adequate clinical and parasitological response), ETF (Early treatment failure), LTF (Late treatment failure, including LPF_Late parasitological failure and LCF_Late clinical treatment). Results: the study was conducted according to the WHO guideline protocols 2009, the results showed that: (1) The ACPR efficacy of artesunate monotherapy were 82.2% and 87.2% in Quang Tri (with cross-border of Laos) and Ninh Thuan (without cross-border) sentinel site, respectively. Benny notes in proportions of LCF of 15.1% and LPF of 2.7% (in Quang Tri), and LCF of 8.5% and LPF of 4.3% (in Ninh Thuan). Both of them were decreasing efficacy with artesunate alone regimes; (2) The ACPR efficacy of ACTs (dihydroartemisinine plus piperaquine) were in ranged 94.8% to 100% during 2007-2011 in Quang Tri, Ninh Thuan, Gia Lai. In which, especially notes in Gia Lai sentinel, there was ETF of 3.4% and LCF of 1.7%, and accompanied with nearly 17% positive parasite on or after D3 post-treatment of ACTs as indirect clinical marker for resistance high risk (WHO definition 2011). Three cases of LCF were corrected by PCR technique and reinfection (new infection) or recrudescence were indetified entirely; (3) Both of artesunate monotherapy and ACTs regimes were high safety, no significant serious side-effects related to these drugs. Conclusions: The efficacy of artesunate alone with treatment failure rate more than 10%, need to be alter for the better, and vice versa, the efficacy of ACTs (dihydroartemisinine plus piperaquine) are extremely high (ACPR = 94.8-100%), ideal for falciparum malaria treatment, but positive parasite on day 3 (prolonged parasite clearance time) > 10% as clinical marker of resistance in the near future. Side-effects of the regimes were reported but did not health care interventions.

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