The effects of diethylcarbamazine on the ultrastructure of microfilariae of Wuchereria bancrofti in vivo and in vitro

Abstract

An ultrastructural study of microfilariae of Wuchereria bancrofti was performed after treatment in vitro and in vivo with diethylcarbamazine citrate (DEC). The morphological alterations produced by treatment in vitro with 5 micro g/ml of DEC were the loss of microfilarial sheaths and lysis of the cytoplasm, with the destruction of all organelles and the formation of several vacuoles, the contents of which presented various degrees of electron-density, or showed an empty appearance. Some of these vacuoles seemed to be extruding from the cytoplasm as apoptotic bodies and others presented organelles inside. Similar alterations were observed after in vivo treatment. At 40 min after treatment of a microfilaremic individual with DEC, almost all microfilariae observed had lost their sheaths; and, in some of them, remains of the microfilarial sheath on the larval surface could be detected. Numerous vacuoles were observed, mainly in the hypodermis and somatic cells, showing organelles inside or an empty appearance. Condensed chromatin was also observed in some somatic cells. At 1 h after treatment of a microfilemic individual with DEC, microfilariae presented drastic morphological alterations, with large vacuoles within somatic cell cytoplasm and complete lysis of all cellular organelles. Therefore, both treatments with DEC in vitro and in vivo had a direct mechanism of action on the microfilariae of W. bancrofti, including organelle damage and apoptosis.

Molecular evidence for apoptosis in microfilariae of Wuchereria bancrofti induced by diethylcarbamazine

“…DEC severely affected microfilariae cells inducing extreme cellular disorganization with abundance of degenerating organelles, large and numerous vacuoles, and nuclear condensation Florêncio and Peixoto 2003;Peixoto et al 2004). Interestingly, although the cellular content in some cells have disappeared, the plasma membrane maintained its integrity .…”

Prior killing of intracellular bacteria Wolbachia reduces inflammatory reactions and improves antifilarial efficacy of diethylcarbamazine in rodent model of Brugia malayi

“…The high levels of reactive oxygen species observed after DEC treatment were due to >80% killing of circulating microfilariae resulting in excessive release of parasite products and Wolbachia-associated molecules and leading to high oxidative stress. Although McGarry et al (2005) reported that iNOS and COX1 mediate mf killing by DEC in vivo in mice intravenously injected with mf, another study has also reported the direct activity of DEC against W. bancrofti microfilariae that results in exsheathment, organelle damage and cytolysis (Peixoto et al 2004), which occur both in vitro and in vivo. Those findings suggest that DEC may have a direct effect on worms beyond its interaction with host-derived pathways as reported here.…”

Arbonematoden - durch Arthropoden übertragbare Nematoden-Infektionen

“…Bestrahlung mit Gammastrahlen bis 10,5 Gy (Gray) tötet Mikrofilarien von Wuchereria bancrofti nicht ab [84]. Behandlung mit 5mg/ml Diehtylcarbamazin in vitro löste Mikrofilarien von Wuchereria bacrofti auf [85], Behandlung mit 2 bis 10 µM Mefloquine (Lariam® zur MalariaProphylaxe) tötete Mikrofilarien von Brugia malayi nach 10 h bis 3 Tagen ab [86].…”