Role of host antibody in the chemotherapeutic action of praziquantel against Schistosoma mansoni: identification of target antigens

Brindley, Paul J.; Strand, Mette; Norden, Amy P.; Sher, Alan

doi:10.1016/0166-6851(89)90001-7

Cited by 143 publications

(153 citation statements)

References 31 publications

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“…This explains why synergistic effect was not substantial in Infected-Treated-Vaccinated group, which was treated before vaccination. This observation is consistent with other experimental findings that showed the enhanced efficacy of the drug in immune sensitised hosts [28,29]. The protection levels in these three groups seem to correlate very well with the proliferative responses.…”

Section: Worm Maturation and Resistancesupporting

confidence: 81%

The effect of vaccinating <i>S. mansoni</i>–infected BALB/c mice either before or after treatment

Yole¹,

Obanda²,

Kithome³

et al. 2008

African Journal of Health Sciences

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Section: Worm Maturation and Resistancesupporting

confidence: 81%

The effect of vaccinating <i>S. mansoni</i>–infected BALB/c mice either before or after treatment

Yole¹,

Obanda²,

Kithome³

et al. 2008

African Journal of Health Sciences

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“…The immune response is an important component of the mechanism of action for praziquantel. [26][27][28][29] Immunosuppression is associated with decreased efficacy of oxamniquine in experimental mice, but reconstitution of these animals with immune serum fully restores effectiveness. While much has been written about the deleterious effect of immune responses to LDL-cholesterol, 30 the pro-inflammatory properties of this form of lipid might be responsible for the effects we see here by altering the immune response to interluminal tissues including those of the parasite.…”

Section: Discussionmentioning

confidence: 99%

Biochemical and Immunologic Predictors of Efficacy of Treatment or Reinfection Risk for Schistosoma Mansoni

Reis¹,

Reis²,

Silva³

et al. 2006

The American Journal of Tropical Medicine and Hygiene

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Abstract. Most Schistosoma mansoni infections are egg-negative after a single dose of oxamniquine. A cohort of 661 infected children was treated at 6-month intervals and assessed for nutritional and parasitological status. Initial biochemical and immunologic markers were measured in a subset of 84 children. All were treated at the start of therapy and at 6 months. Immunoglobulins only served as markers for active infection. No markers were predictive of cure or reinfection, except initial infection intensity and serum low-density lipoprotein. Ten percent were persistently infected and had no change in infection intensity at any time-point. Several factors suggest that this group was biologically different. In addition to failing to reduce their worm burden, they had significantly higher initial intensity of infection (100 versus 65 eggs/g, P ‫ס‬ 0.001) and significantly lower initial serum low-density lipoprotein (72 versus 104 mg/dL, P ‫ס‬ 0.045). The biologic plausibility of this observation is discussed.

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“…5 However, the reality of these reports is difficult to establish because it is often difficult to distinguish between host factors and parasite factors when patients are not cured of schistosomiasis with normally effective doses. First, since the host immune system plays an active role in the process of killing PZQ-damaged worms, 6 normal parasites might survive treatment in immunocompromised hosts. In vivo studies can also be confounded by the fact that PZQ is less effective in killing immature parasites, 7 such that a wide range of host factors inhibiting development of the parasites can cause an apparent decrease in drug efficacy.…”

mentioning

confidence: 99%

Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers.

Ismail¹,

Botros²,

Metwally³

et al. 1999

Am J Trop Med Hyg

431

270

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Abstract. Recent evidence suggest that resistance to praziquantel (PZQ) may be developing. This would not be surprising in countries like Egypt where the drug has been used aggressively for more that 10 years. The classic phenotype of drug resistance is a significant increase in the 50% effective dose value of isolates retrieved from patients not responding to the drug. In a previous publication, we reported that such phenotypes have been isolated from humans infected with Schistosoma mansoni. Since the action of PZQ may be dependent upon the drug and host factors, most notably the immune system, we analyzed the quantitative effects of PZQ on single worms that differed in their response to PZQ when maintained in mice. Our hypothesis was that the in vitro action of the drug would correlate with it in vivo action. We confirmed this hypothesis and conclude that the in vitro action of the drug is related to its in vivo action. Knowing this relationship will assist in our ability to detect or survey for the PZQ resistant phenotype in human populations.Praziquantel (PZQ) is used for the treatment of infections caused by Schistosoma spp. 1 In a number of regions, including much of Egypt, PZQ has been copiously used, and the impact of the drug on schistosome infections has been significant. 2,3 In the laboratory, exposure of schistosomes to subcurative doses of PZQ over generations resulted in drugresistant schistosomes, 4 demonstrating the possibility of resistance arising in the field. Indeed, reports of resistance in the field have recently appeared. 5 However, the reality of these reports is difficult to establish because it is often difficult to distinguish between host factors and parasite factors when patients are not cured of schistosomiasis with normally effective doses. First, since the host immune system plays an active role in the process of killing PZQ-damaged worms, 6 normal parasites might survive treatment in immunocompromised hosts. In vivo studies can also be confounded by the fact that PZQ is less effective in killing immature parasites, 7 such that a wide range of host factors inhibiting development of the parasites can cause an apparent decrease in drug efficacy. Variability of host PZQ metabolism can also cause variability of efficacy. 8 In an effort to minimize the variability of these host factors, parasites isolated from patients not cured by antischistosomal drugs have been used to establish experimental infections in less-variable laboratory animal hosts. 9 If infections produced by these isolates are not cured by normal doses of PZQ, it suggests that the decreased responsiveness of the isolates is due to worm factors rather than host factors. However, this type of assessment is a rather toilsome process.Despite the dependence of PZQ on the host immune system for killing the parasites in vivo, PZQ has dramatic, measurable effects on schistosomes in vitro. The three hallmark effects are contraction of the worm musculature, 10 an influx of calcium into the worm, 11 and disruption of the tegument...

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Role of host antibody in the chemotherapeutic action of praziquantel against Schistosoma mansoni: identification of target antigens

Cited by 143 publications

References 31 publications

The effect of vaccinating <i>S. mansoni</i>–infected BALB/c mice either before or after treatment

The effect of vaccinating <i>S. mansoni</i>–infected BALB/c mice either before or after treatment

Biochemical and Immunologic Predictors of Efficacy of Treatment or Reinfection Risk for Schistosoma Mansoni

Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers.

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