Phần 1. Cập nhật thông tin về hiệu lực thuốc sốt rét artesunate-mefloquine trong điều trị sốt rét do Plasmodium falciparum đa kháng thuốc
Trong bối cảnh sốt rét do Plasmodium falciparum đa kháng thuốc, kể cả thuốc có hiệu lực cao, kể cả thuốc đầu tay hay thuốc lựa chọn ưu tiên (first-line treatment/ first of choice) như dihydroartemisinine-piperaquine (Arterakine/ CV-Artecan) cũng đã cho thấy thuốc trở nên giảm hiệu lựcở một số tỉnh miền Trung Tây Nguyên (Đăk Nông, Gia Lai, Đăk Lăk, Quảng Nam, Khánh Hòa, Ninh Thuận) và Nam bộ (Bình Phước) thì việc nghiên cứu một loại thuốc mới thay thế là rất cần thiết hiện nay nhằm giảm gánh nặng bệnh tật, giảm biến chứng, giảm tử vong, giảm kháng thuốc lan rộng và nâng cao sức khỏe cho bệnh nhân.
Một trong những liệu pháp thuốc đó chính là phối hợp artesunate-mefloquine (ASMQ) với dạng chế phẩm viên nén, viên nang đóng vỉ rời hay trong cùng một viên thuốc. Tất cả đều cho hiệu lực chữa khỏi cao và hiệu quả điều trị cao, tình dung nạp thuốc tốt và tác dụng ngoại ý không đáng kể.
Liệu pháp thuốc phối hợp có thành phần artemisinin (ACTs) được khuyến cáo điều trị ưu tiên đối với sốt rét do Plasmodium falciparum chưa biến chứng tại hầu hết quốc gia và vũng lãnh thổ trên toàn cầu và kết hợp liều cố định được Tổ chức Y tế thế giới đưa ra từ năm 2010 đến nay vẫn còn áp dụng ưu tiên với năm loại thuốc phối hợp ACTs (WHO, 2010).
Trong một thử nghiệm ngẫu nhiên, nhãn mở tại các phòng khám ở Myanmar nhằm so sánh hiệu quả của bốn loại ACTs liều cố định được TCYTTG khuyến cáo gồm mefloquine-artesunate (n = 169), artesunat-amodiaquin (n = 155), dihydroartemisinin-piperaquine (n = 161), artemether-lumefantrin (n = 162) và artesunate-mefloquine liều rời (n = 161) ở người lớn và trẻ em. Theo dõi liệu trình 63 ngày cho thấy tỉ lệ tái phát lần lượt là 0%, 1,3%, 1,3%, 1,4% và 9,4% lần lượt ở các nhóm điều trị với mefloquin-artesunat (viên phối hợp), artesunat-mefloquin (liều viên rời), dihydroartemisinin-piperaquin (DHA-PPQ), artemether-lumefantrin và artesunat-amodiaquin. Nghiên cứu cũng cho thấy artesunat-mefloquin có hiệu lực cao nhất trong điều trị bệnh nhân sốt rét do P. falciparum . Một nghiên cứu so sánh liều cố định mefloquin-artesunat (n = 25) và liều viên rời (n = 25) trên bệnh nhân nhiễm Plasmodium falciparum chưa biến chứng ở người lớn tại Thái Lan theo dõi 28 ngày cho thấy cả hai phác đồ đều được dung nạp tốt. Không có tác dụng ngoại ý nào liên quan đến thuốc và không có thay đổi đáng kể về các thông số huyết học, sinh hóa, hoặc khoảng PR và khoảng thời gian phức bộ QRS trên điện tâm đồ.
Phác đồ ASMQ liệu trình 3 ngày hiện đang được sử dụng ở Campuchia tại những vùng có thất bại điều trị với thuốc DHA-PPQ và cho tỷ lệ chữa khỏi trên 99% (Chanaki và cs., 2013). Một thử nghiệm lâm sàng được thực hiện để đánh giá hiệu quả, tính an toàn và dược động học của liều kết hợp cố định ASMQ trong điều trị bệnh nhân nhiễm Plasmodium falciparum tại Ấn Độ cho thấy thuốc có hiệu quả và được dung nạp tốt đường uống trong điều trị sốt rét P. falciparum không biến chứng ở những vùng có kháng chloroquin.
Nghiên cứu so sánh các thuốc phối hợp liều cố định artesunat-mefloquin và artemether- lumefantrin để điều trị sốt rét Plasmodium falciparum không biến chứng ở trẻ dưới 5 tuổi trong vùng cận sa mạc Sahara, châu Phi. Kết quả nghiên cứu cho thấy tỷ lệ điều trị khỏi (ACPR) sau hiệu chỉnh PCR ở ngày 63 là 90,9% (370 bệnh nhân) trong nhóm ASMQ và 89,7% (365 bệnh nhân) trong nhóm artemether-lumefantrin.
Các tác giả cho rằng ASMQ hiệu quả và an toàn và là lựa chọn điều trị quan trọng đối với trẻ em dưới 5 tuổi bị sốt rét do P. falciparum không biến chứng ở châu Phi. Một nghiên cứu khác do nhóm tác giả Marielle K và cộng sự (2010) tiến hành với công thức liều dùng cho trẻ em mắc sốt rét. Thử nghiêm lâm sàng đánh giá hiệu lực, an toàn và tính dung nạp của thuốc ASMQ trong viên nang (granule co-blister tablet formulation). Tổng số 71 bệnh nhi tuổi từ 1-13 mắc sốt rét chưa biến chứng được chia thành hai nhóm theo cân nặng: 10-20 kg, nhóm trẻ em nhỏ dùng viên nang (n = 41); 20-40 kg, nhóm trẻ lớn hơn (n = 30). Tất cả được điều trị mỗi ngày một lầntrong 3 ngày. Trên nhóm trẻ em nhỏ nhận uống loại viên nang và nhóm còn lại dùng viên nén. Tỷ lệ chữa khỏi sau hiệu chỉnh PCR vào ngày D28 được đánh giá thấy không có sự tái xuất hiện KSTSR trong máu, nên tỷ lệ này là 100% theo phân tích per protocol, tỷ lệ chữa khỏi theo phân tích intention-to-treat là 95% trên nhóm dùng viên nang và 97% trên nhóm dùng viên nén.
Tác dụng ngoại ý hay gặp nhất là nôn mửa (17%), đau bụng (11%) và nhức đầu (17%). Nghiên cứu này xác định rắng thuốc có hiệu lực và tính an toàn, dung nạp thuốc tốt với chế phẩm dạng viên nang trong điều trị trẻ em châu Phi. Tài liệu tham khảo:
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Activities of artesunate and primaquine against asexual- and sexual-stage parasites in falciparum malaria.
Pukrittayakamee S, Chotivanich K, Chantra A, Clemens R, Looareesuwan S, White NJ.Antimicrob Agents Chemother. 2004 Apr;48(4):1329-34.PMID:15047537 Free PMC Article Similar articles Select item 15115124 45.
Six-years monitoring the efficacy of the combination of artesunate and mefloquine for the treatment of uncomplicated falciparum malaria.
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Randomized, multicentre assessment of the efficacy and safety of ASAQ--a fixed-dose artesunate-amodiaquine combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria.
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Efficacy of oral and intravenous artesunate in male Tanzanian adults with Plasmodium falciparum malaria and in vitro susceptibility to artemisinin, chloroquine, and mefloquine.
Alin MH, Kihamia CM, Bjorkman A, Bwijo BA, Premji Z, Mtey GJ, Ashton M.Am J Trop Med Hyg. 1995 Dec;53(6):639-45.PMID:8561267 Similar articles Select item 27221542 48.
Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy: a systematic review and meta-analysis of individual patient data.
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Artemisinin resistance containment project in Thailand. II: Responses to mefloquine-artesunate combination therapy among falciparum malaria patients in provinces bordering Cambodia.
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Pyronaridine-artesunate versus mefloquine plus artesunate for malaria.
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Adverse effects of mefloquine for the treatment of uncomplicated malaria in Thailand: A pooled analysis of 19, 850 individual patients.
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An open-label, randomised study of dihydroartemisinin-piperaquine versus artesunate-mefloquine for falciparum malaria in Asia.
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Efficacy, safety and tolerability of artesunate-mefloquine in the treatment of uncomplicated Plasmodium falciparum malaria in four geographic zones of Nigeria.
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Gametocytemia in falciparum malaria treated with amodiaquine or artesunate].
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Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum.
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Efficacy of Different Primaquine Regimens to Control Plasmodium falciparum Gametocytemia in Colombia.
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Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.
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Artemisinin derivatives and malaria: useful, in combination with other antimalarials.
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A randomized trial of artesunate-mefloquine versus artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Mali.
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Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study.
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Single day mefloquine-artesunate combination in the treatment of multi-drug resistant falciparum malaria.
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Therapeutic efficacy and effects of artesunate-amodiaquine and artemether-lumefantrine on malaria-associated anaemia in Nigerian children aged two years and under.
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Population pharmacokinetic assessment of a new regimen of mefloquine used in combination treatment of uncomplicated falciparum malaria.
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Efficacy and safety of an artesunate/mefloquine combination, (artequin) in the treatment of uncomplicated P. falciparum malaria in Kenya.
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Comparative study of the effectiveness and pharmacokinetics of two rectal artesunate/oral mefloquine combination regimens for the treatment of uncomplicated childhood falciparum malaria.
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Efficacy of mefloquine treatment and genetic profiles in uncomplicated Plasmodium falciparum malaria in southern Lao PDR.
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Distribution of mefloquine in the blood of Thai patients with acute uncomplicated falciparum malaria following administration of therapeutic doses of artesunate.
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Efficacy and tolerability of four antimalarial combinations in the treatment of uncomplicated Plasmodium falciparum malaria in Senegal.
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Editorial commentary: single-dose primaquine as gametocytocidal treatment in patients with uncomplicated falciparum malaria.
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Treatment of patients with recrudescent falciparum malaria with a sequential combination of artesunate and mefloquine.
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Therapeutic efficacy of artemether-lumefantrine and artesunate-mefloquine for treatment of uncomplicated Plasmodium falciparum malaria in Luang Namtha Province, Lao People's Democratic Republic.
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Randomized comparison of chloroquine plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in the Lao People's Democratic Republic.
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Efficacy of non-artemisinin- and artemisinin-based combination therapies for uncomplicated falciparum malaria in Cameroon.
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Therapeutic efficacy of fixed dose artesunate-mefloquine for the treatment of acute, uncomplicated Plasmodium falciparum malaria in Kampong Speu, Cambodia.
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