Anti-parasitic drugs may achieve their therapeutic effect either by direct activity against the pathogenic organism, or by altering host factors which lead to parasite killing. In this review, we discuss the evidence for an indirect mode of action for one major anti-filarial drug, diethylcarbamazine (DEC). The interpretation most consistent with existing data is that DEC alters arachidonic acid metabolism in microfilariae and in host endothelial cells. These changes may result in vasoconstriction and amplified endothelial adhesion leading to immobilization of microfilarial parasites, enhanced adherence and cytotoxic activity by host platelets and granulocytes. These events would represent activation of the innate, non-specific immune system, independent of the adaptive, antigen-specific, immune response. This model explains the paradox between rapid clearance in vivo and the lack of an in vitro effect, as well as the efficacy of DEC in non-immune animals. It may also account for the inconsistencies in the effects of DEC against different filariae in different host species. In addition, we discuss the significant side-effects often associated with treatment of heavily infected patients, and the longer-term changes in T-cell reactivity and the host-parasite relationship which follow successful treatment with DEC.
Seven microfilaraemic and five amicrofilaraemic cats which had been repeatedly infected with Brugia pahangi were challenged along with normal cats 28, 14 and 1 day before autopsy. The lymphatics of the amicrofilaraemic cats contained no female adult worms originating from the repeat infections and only two adult males (both from the same cat). Only 5.2% of the worms in the control cats were recovered from the amicrofilaraemic cats. Most of the challenge worms were killed in the first 24 h. The microfilaraemic cats all contained fertile adult male and female worms derived from the repeated infection but in such low numbers as to indicate considerable resistance to infection. Compared to their controls 26.4% of the challenge worms were recovered. Analysis of the life-cycle stages recovered showed that in both groups there was attrition of all stages and that although a number of worms reached L5 these were all killed later in the amicrofilaraemic cats.
The clinical and autopsy findings of a two and a half year-old infant with Toxocara sp. infection of the brain and granulomatous lesions in the liver are reported. The cause of death was non-accidental injury. The relationship between Toxocara infection and behavioural disorders is discussed.
A set of cross-reactive antigens is described which are present in somatic extracts and in-vitro secretions of the filarial nematodes Brugia pahangi and B. malayi. A monoclonal antibody reactive with a repeating epitope on these molecules readily detects circulating antigen in the serum of animals infected with lymphatic filariae, using either an immunoradiometric assay or enzyme-linked immunosorbent assay (ELISA). This epitope has the immunological reactivity and chemical characteristics of the phosphorylcholine (PC) hapten. The anti-PC monoclonal has been used to define the antigens bearing this epitope, and in chromatographic studies on material from extracts of Brugia adult worms, a heterogeneous profile of PC-positive molecules are found. In sera from Brugia-infected jirds, an antigen with a native molecular weight of approximately 500,000 is observed, which displays limited sensitivity to protease degradation. However, denatured samples on Western blots show a major parasite circulating antigen of Mr 90,000. The detection of this antigen in the presence of excess host antibody is also demonstrated, taking advantage of the stability of the target epitope to a range of treatments designed to dissociate and eliminate immune complexes.
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