Weitzman Rachel, Calfon-Peretz Ortal, Saha Trishna, Bloch Naamah, Ben Zaken Karin, Rosenfeld Avi, Amitay Moshe, Samson Abraham O
Bioinformatic Department, Jerusalem College of Technology, Jerusalem 9372115, Israel.
Drug Discovery Lab, Azrieli Faculty of Medicine, Bar Ilan University, Safed 1311502, Israel.
J Clin Med. 2022 Jan 31;11(3):781. doi: 10.3390/jcm11030781.
Malaria is a prevalent parasitic disease that is estimated to kill between one and two million people-mostly children-every year. Here, we query PubMed for malaria drug resistance and plot the yearly citations of 14 common antimalarials. Remarkably, most antimalarial drugs display cyclic resistance patterns, rising and falling over four decades. The antimalarial drugs that exhibit cyclic resistance are quinine, chloroquine, mefloquine, amodiaquine, artesunate, artemether, sulfadoxine, doxycycline, halofantrine, piperaquine, pyrimethamine, atovaquone, artemisinin, and dihydroartemisinin. Exceptionally, the resistance of the two latter drugs can also correlate with a linear rise. Our predicted antimalarial drug resistance is consistent with clinical data reported by the Worldwide Antimalarial Resistance Network (WWARN) and validates our methodology. Notably, the cyclical resistance suggests that most antimalarial drugs are sustainable in the end. Furthermore, cyclic resistance is clinically relevant and discourages routine monotherapy, in particular, while resistance is on the rise. Finally, cyclic resistance encourages the combination of antimalarial drugs at distinct phases of resistance.
疟疾是一种普遍存在的寄生虫病，据估计每年导致100万至200万人死亡，其中大多数是儿童。在此，我们在PubMed上查询疟疾耐药性，并绘制了14种常见抗疟药的年度引用次数。值得注意的是，大多数抗疟药呈现出周期性耐药模式，在40年里有起有落。呈现周期性耐药的抗疟药有奎宁、氯喹、甲氟喹、阿莫地喹、青蒿琥酯、蒿甲醚、磺胺多辛、强力霉素、卤泛群、哌喹、乙胺嘧啶、阿托伐醌、青蒿素和双氢青蒿素。例外的是，后两种药物的耐药性也可能与线性上升相关。我们预测的抗疟药耐药性与全球抗疟药耐药性网络（WWARN）报告的临床数据一致，并验证了我们的方法。值得注意的是，周期性耐药表明大多数抗疟药最终是可持续的。此外，周期性耐药在临床上具有相关性，尤其在耐药性上升时不鼓励常规单一疗法。最后，周期性耐药促使在耐药的不同阶段联合使用抗疟药。
