Volkmann Lars, Fischer Kerstin, Taylor Mark, Hoerauf Achim
Department of Helminthology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Trop Med Int Health. 2003 May;8(5):392-401. doi: 10.1046/j.1365-3156.2003.01040.x.
The symbiosis of filarial nematodes and rickettsial Wolbachia endobacteria has been exploited as a target for antibiotic therapy of filariasis. Depletion of Wolbachia after tetracycline treatment results in filarial sterility because of interruption of embryogenesis and inhibits larval development and adult worm viability. The aim of this study was to investigate if antibiotic intervention of BALB/c mice infected with the rodent filaria Litomosoides sigmodontis with rifampicin or the combination of rifampicin and doxycycline can be used to shorten the treatment period. Both regimens, when given over a period of 14 days initiated with infection, were sufficient to deplete Wolbachia as evidenced by immunohistology and semiquantitative PCR. Worm development and filarial load were significantly reduced in experiments followed up until 63 days p.i. The therapy inhibited embryogenesis and led to filarial sterility. In contrast, treatment with doxycycline alone for 21 days led only to a modest reduction of Wolbachia, filarial growth retardation, worm viability and fertility. In conclusion, the combination of antirickettsial drugs could be used as a suitable tool to explore the minimum duration of therapy required for the depletion of Wolbachia in parasitized hosts subsequent to the onset of patency in human and animal filariasis and the prevention of adverse reactions in human infections.
丝虫线虫与立克次氏体沃尔巴克氏体共生菌的共生关系已被用作丝虫病抗生素治疗的靶点。四环素治疗后沃尔巴克氏体的消耗导致丝虫不育,原因是胚胎发生中断,并抑制幼虫发育和成虫活力。本研究的目的是调查用利福平或利福平和强力霉素联合对感染啮齿动物丝虫锡兰布鲁线虫的BALB/c小鼠进行抗生素干预是否可用于缩短治疗期。从感染开始给予14天的这两种治疗方案,均足以消耗沃尔巴克氏体(免疫组织学和半定量PCR证明)。在感染后63天进行随访的实验中,蠕虫发育和丝虫负荷显著降低。该治疗抑制胚胎发生并导致丝虫不育。相比之下,单独用强力霉素治疗21天仅导致沃尔巴克氏体适度减少、丝虫生长迟缓、蠕虫活力和繁殖力下降。总之,抗立克次氏体药物联合可作为一种合适的工具,用于探索在人类和动物丝虫病出现明显症状后,在寄生宿主中消耗沃尔巴克氏体所需的最短治疗期,以及预防人类感染中的不良反应。