Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Room 3E-10C, Rockville, MD 20852, USA.
Malar J. 2010 Dec 23;9:374. doi: 10.1186/1475-2875-9-374.
The loss of chloroquine due to selection and spread of drug resistant Plasmodium falciparum parasites has greatly impacted malaria control, especially in highly endemic areas of Africa. Since chloroquine removal a decade ago, the guidelines to treat falciparum malaria suggest combination therapies, preferentially with an artemisinin derivative. One of the recommended partner drugs is amodiaquine, a pro-drug that relies on its active metabolite monodesethylamodiaquine, and is still effective in areas of Africa, but not in regions of South America. Genetic studies on P. falciparum parasites have shown that different pfcrt mutant haplotypes are linked to distinct levels of chloroquine and amodiaquine responses. The pfcrt haplotype SVMNT (termed after the amino acids from codon positions 72-76) is stably present in several areas where amodiaquine was introduced and widely used. Parasites with this haplotype are highly resistant to monodesethylamodiaquine and also resistant to chloroquine. The presence of this haplotype in Africa was found for the first time in 2004 in Tanzania and a role for amodiaquine in the selection of this haplotype was suggested. This commentary discusses the finding of a second site in Africa with high incidence of this haplotype. The >50% SVMNT haplotype prevalence in Angola represents a threat to the rise and spread of amodiaquine resistance. It is paramount to monitor pfcrt haplotypes in every country currently using amodiaquine and to re-evaluate current combination therapies in areas where SVMNT type parasites are prevalent.
由于耐药恶性疟原虫寄生虫的选择和传播，氯喹的损失对疟疾控制产生了重大影响，尤其是在非洲高度流行的地区。自氯喹十年前被淘汰以来，治疗恶性疟疾的指南建议采用联合疗法，最好使用青蒿素衍生物。推荐的联合用药之一是阿莫地喹，一种前药，依赖其活性代谢物单脱乙基阿莫地喹，在非洲地区仍然有效，但在南美洲地区无效。对恶性疟原虫寄生虫的遗传研究表明，不同的 pfcrt 突变体单倍型与氯喹和阿莫地喹反应的不同水平相关联。pfcrt 单倍型 SVMNT（以密码子位置 72-76 的氨基酸命名）在几个引入和广泛使用阿莫地喹的地区稳定存在。具有这种单倍型的寄生虫对单脱乙基阿莫地喹高度耐药，也对氯喹耐药。该单倍型于 2004 年首次在坦桑尼亚发现，有人认为阿莫地喹在该单倍型的选择中起了作用。本文讨论了在非洲发现第二个高发生率该单倍型的地点。安哥拉超过 50%的 SVMNT 单倍型流行率对阿莫地喹耐药性的出现和传播构成了威胁。监测目前使用阿莫地喹的每个国家的 pfcrt 单倍型，并在 SVMNT 型寄生虫流行的地区重新评估当前的联合治疗方案至关重要。
