Intensity of transmission and spread of gene mutations linked to chloroquine and sulphadoxine-pyrimethamine resistance in falciparum malaria
Intensity of transmission and spread of gene mutations linked to chloroquine and sulphadoxine-pyrimethamine resistance in falciparum malaria
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DOI：
10.1016/s0020-7519(03)00156-5
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发表时间：
2003-09-15
影响因子：
4
通讯作者：
D'Alessandro, U
中科院分区：
文献类型：
--
作者：
Talisuna, AO;Langi, P;D'Alessandro, U
每次感染的疟原虫克隆数——疟原虫克隆的多重性——受传播强度的影响，多重性随着传播的增加而增加。这影响了寄生虫性重组的频率，如果涉及到不同基因的几个突变，就会破坏耐药基因型。因此，疟疾传播强度对耐药性传播的影响可能因涉及的基因数量而异。在这里，我们表明，与低传播相比，中高传播与氯喹耐药相关的突变风险降低20-100倍，与磺胺嘧啶-乙胺嘧啶耐药相关的突变风险增加6-17倍。这与氯喹耐药的多基因基础和磺胺-乙胺嘧啶耐药的单基因基础的假设是一致的。降低传播强度可以减缓耐药性的传播。然而，降低到临界阈值以下（例如，当2-9岁儿童中的寄生虫流行率约为60-80%时）可能会加速对氯喹以及可能对其他多基因药物组合的耐药性的传播，这是自相矛盾的。我们的发现对疟疾控制具有重要意义，因为耐药性的增加对死亡率有重大影响。(C) 2003澳大利亚寄生虫学学会Elsevier Ltd.出版。版权所有。
The number of malaria parasite clones per infection-multiplicity of parasite clones-is affected by the transmission intensity, multiplicity increases with increasing transmission. This affects the frequency of parasites' sexual recombination and, if several mutations in different genes are involved, can break down drug resistant genotypes. Therefore, the effects of malaria transmission intensity on the spread of drug resistance could vary depending on the number of genes involved. Here we show that, compared to low transmission, intermediate-high transmission is associated with a 20-100-fold lower risk for the mutations linked to chloroquine resistance and a 6-17 times higher risk for those linked to sulphadoxine-pyrimethamine resistance. This is consistent with the hypothesis of a multigenic basis for chloroquine resistance and a monogenic basis for that of sulphadoxine-pyrimethamine. Reducing transmission intensity could slow the spread of resistance. However, a reduction below a critical threshold (e.g. when parasite prevalence in children 2-9 years old is around 60-80%) could, paradoxically, accelerate the spread of resistance to chloroquine and possibly to other drug combinations whose basis is multigenic. Our findings have important implications for malaria control because increasing drug resistance has a substantial impact on mortality. (C) 2003 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.